(44.192.10.166) 您好!臺灣時間:2021/03/06 04:21
字體大小: 字級放大   字級縮小   預設字形  
回查詢結果

詳目顯示:::

我願授權國圖
: 
twitterline
研究生:張詠婷
研究生(外文):Yung-Ting Chang
論文名稱:軟珊瑚衍生之海洋天然物藉由提高氧化壓力而誘導口腔癌細胞凋亡之研究
論文名稱(外文):Soft Coral-Derived Marine Natural Products Enhance Oxidative Stress-Mediated Apoptosis in Oral Cancer Cells
指導教授:廖志中廖志中引用關係
指導教授(外文):Chih-Chuang Liaw
學位類別:博士
校院名稱:國立中山大學
系所名稱:海洋生物科技博士學位學程
學門:自然科學學門
學類:海洋科學學類
論文種類:學術論文
論文出版年:2018
畢業學年度:106
語文別:英文
論文頁數:105
中文關鍵詞:sinuleptolidesinularin軟珊瑚細胞凋亡氧化壓力活性氧口腔癌海洋天然物
外文關鍵詞:apoptosissoft coralsinularinsinuleptolidemarine natural productsoral cancerROSoxidative stress
相關次數:
  • 被引用被引用:0
  • 點閱點閱:77
  • 評分評分:系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔系統版面圖檔
  • 下載下載:0
  • 收藏至我的研究室書目清單書目收藏:0
在過去幾年中,分子生物學技術的發展強調了感染人類乳突病毒(human papillomavirus; HPV)以及使用檳榔、煙草和酒精的生活習慣等,皆可能透過導致染色體不穩定性或遺傳物質突變成為癌症的高風險因子,在口腔癌的癌變過程佔了很大的因素。病患的年齡及病兆的位置都會影響口腔癌的預後效果,目前的治療方式以手術切除搭配化學放療為主,但由於手術切除口腔組織影響吞嚥或咀嚼功能甚廣,且化學療法引起諸多嚴重的副作用,導致口腔癌的癌症五年存活率多年以來一直低於50%。因此找尋有效且低副作用的治療藥物與策略有其醫療價值。本論文探討了兩種分離自軟珊瑚之海洋天然物sinuleptolide和sinularin在口腔癌細胞株中具有調節細胞凋亡和細胞週期停滯的現象並且發現與氧化壓力有關。在藥物處理後出現誘導抑制細胞增殖、使細胞外觀具有凋亡形態、產生活性氧(reactive oxygen species; ROS)及粒線體超氧化物、細胞凋亡過程中磷脂醯絲胺酸(phosphatidylserine)外翻現象(annexin V染色法)和藉由觀測gamma H2A histone family member X (γH2AX)蛋白所偵測到的DNA損傷;此外,這些變化在正常細胞中皆有較低的毒性,且透過預處理活性氧抑制劑N-乙醯半胱氨酸(N-acetylcysteine; NAC)能防制毒性。綜合上述,本研究發現sinuleptolide和sinularin誘導了氧化壓力所造成的抗細胞增殖、G2/M細胞週期停滯,並且導致口腔癌細胞凋亡,展現海洋天然藥物用於氧化壓力治療法的抗癌潛力。
Over the past few years, the development of molecular biology techniques has highlighted the high cancerous risk factors such as human papillomavirus (human papillomavirus; HPV) infection, using betel nuts, tobacco and alcohol. These habits may cause chromosomal instability or genetic mutations are responsible for oral cancer carcinogenesis process. The patients'' age and the location of tumor may affect the prognosis of oral cancer. The current treatment of oral cancer is surgical resection with adjuvant chemotherapy, but this surgical removal of tumor tissues affect swallowing and chewing function and chemotherapy usually generate side effects. The five-year survival rate of oral cancer has been below 50% for many years. Therefore, searching for effective anticancer drugs and strategies with lower side effects is valuable. This thesis investigated the anticancer effects of two marine natural products (sinuleptolide and sinularin) isolated from soft corals in terms of regulating apoptosis and cell cycle arrest in association with oxidative stress of oral cancer cell lines. Antiproliferation, apoptosis-like morphology, reactive oxygen species (ROS)/mitochondrial superoxide generation, annexin V-based apoptosis, and gamma H2A histone family member X (γH2AX)-based DNA damage were dose-responsively induced after treatments; moreover, all these changes were less harmful in normal cells and were rescued by ROS scavenger (N-acetylcysteine; NAC) pretreatment. Taken together, this thesis demonstrates that sinuleptolide and sinularin induce oxidative stress-mediated antiproliferation, G2/M arrest, and apoptosis against oral cancer cells and it presents potential oxidative stress-based anticancer therapy using these marine natural products.
論文審定書......i
誌謝......ii
摘要......iii
Abstract......iv
Contents......vi
List of Figures......xi
Chapter 1 Introduction......1
1.1 Oral cancer......1
1.2 Treatments of oral cancer......3
Chapter 2 Literature Review......5
2.1 New strategy for the treatment......5
2.2 Oxidation stress as anticancer strategy......5
2.3 Natural products for anticancer agents......6
Chapter 3 Experimental Section......9
3.1 Cell cultures and chemicals......9
3.2 Measurement of cell viability......10
3.3 Measurement of cell cycle distribution......11
3.4 Measurement of apoptosis by annexin V/propidium iodide (PI)......11
3.5 Measurement of apoptosis by poly (ADP-ribose) polymerase (PARP)......12
3.6 Measurement of intracellular reactive oxygen species (ROS) level......12
3.7 Measurement of mitochondrial membrane potential (MMP)......13
3.8 Measurement of DNA damage by comet assay......13
3.9 Measurement of DNA damage by gamma H2A histone family member X (γH2AX) assay......13
3.10 Mitochondrial superoxide production......14
3.11 Western blotting for G2/M arrest signaling......15
3.12 Apoptosis analysis by pancaspase......15
3.13 Apoptosis analysis by western blotting of caspases......16
3.14 Statistical analysis......16
Chapter 4 Sinuleptolide Inhibits Proliferation of Oral Cancer Cells Ca9-22 Involving Apoptosis, Oxidative Stress, and DNA Damage......18
4.1 Introduction......18
4.2 Results......19
4.2.1 Cell growth status in sinuleptolide treatment......19
4.2.2 Cell cycle status in sinuleptolide treatment......19
4.2.3 Apoptosis status in sinuleptolide treatment......20
4.2.4 ROS status in sinuleptolide treatment......20
4.2.5 MMP status in sinuleptolide treatment......21
4.2.6 DNA damage status in sinuleptolide treatment......21
4.3 Discussion......23
4.4 Illustrations......27
Chapter 5 Reactive Oxygen Species Mediate Soft Corals-Derived Sinuleptolide-Induced Antiproliferation and DNA Damage in Oral Cancer Cells......34
5.1 Introduction......34
5.2 Results......35
5.2.1 NAC effect on sinuleptolide-induced cell killing......35
5.2.2 NAC effect on sinuleptolide-induced morphology change......35
5.2.3 NAC effect on sinuleptolide-induced ROS generation......36
5.2.4 NAC effect on sinuleptolide-induced mitochondrial superoxide generation......36
5.2.5 NAC effect on sinuleptolide-induced γH2AX/PI-based DNA damage......37
5.3 Discussion......38
5.4 Illustrations......42
Chapter 6 Sinularin Induces Oxidative Stress-Mediated G2/M Arrest and Apoptosis in Oral Cancer Cells......48
6.1 Introduction......48
6.2 Results......49
6.2.1 Cell viability of sinularin-treated oral cancer cells and NAC pretreatment effect......49
6.2.2 ROS generation of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......50
6.2.3 Cell morphology of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......50
6.2.4 Cell cycle changes of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......51
6.2.5 G2/M regulatory proteins of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......51
6.2.6 Annexin V/PI-based apoptosis of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......52
6.2.7 Caspases-based apoptosis of sinularin-treated oral cancer cells Ca9-22 and NAC pretreatment effect......53
6.3 Discussion......55
6.4 Illustrations......58
Chapter 7 Conclusion......67
References......71
References
1.Silverman S., Jr., Gorsky M.: Epidemiologic and demographic update in oral cancer: California and national data--1973 to 1985. J Am Dent Assoc 1990, 120(5):495-499.
2.Lingen M. W., Kalmar J. R., Karrison T., Speight P. M.: Critical evaluation of diagnostic aids for the detection of oral cancer. Oral Oncol 2008, 44(1):10-22.
3.Thompson L.: World health organization classification of tumours: Pathology and genetics of head and neck tumours. Ear Nose Throat J 2006, 85(2):74.
4.Kumar M., Nanavati R., Modi T. G., Dobariya C.: Oral cancer: Etiology and risk factors: A review. J Cancer Res Ther 2016, 12(2):458-463.
5.Global Burden of Disease Cancer Collaboration, Fitzmaurice C., Allen C., Barber R. M., Barregard L., Bhutta Z. A., Brenner H., Dicker D. J., Chimed-Orchir O., Dandona R., Dandona L., Fleming T., Forouzanfar M. H., Hancock J., Hay R. J., Hunter-Merrill R., Huynh C., Hosgood H. D., Johnson C. O., Jonas J. B., Khubchandani J., Kumar G. A., Kutz M., Lan Q., Larson H. J., Liang X., Lim S. S., Lopez A. D., MacIntyre M. F., Marczak L., Marquez N., Mokdad A. H., Pinho C., Pourmalek F., Salomon J. A., Sanabria J. R., Sandar L., Sartorius B., Schwartz S. M., Shackelford K. A., Shibuya K., Stanaway J., Steiner C., Sun J., Takahashi K., Vollset S. E., Vos T., Wagner J. A., Wang H., Westerman R., Zeeb H., Zoeckler L., Abd-Allah F., Ahmed M. B., Alabed S., Alam N. K., Aldhahri S. F., Alem G., Alemayohu M. A., Ali R., Al-Raddadi R., Amare A., Amoako Y., Artaman A., Asayesh H., Atnafu N., Awasthi A., Saleem H. B., Barac A., Bedi N., Bensenor I., Berhane A., Bernabe E., Betsu B., Binagwaho A., Boneya D., Campos-Nonato I., Castaneda-Orjuela C., Catala-Lopez F., Chiang P., Chibueze C., Chitheer A., Choi J. Y., Cowie B., Damtew S., das Neves J., Dey S., Dharmaratne S., Dhillon P., Ding E., Driscoll T., Ekwueme D., Endries A. Y., Farvid M., Farzadfar F., Fernandes J., Fischer F., TT G. Hiwot, Gebru A., Gopalani S., Hailu A., Horino M., Horita N., Husseini A., Huybrechts I., Inoue M., Islami F., Jakovljevic M., James S., Javanbakht M., Jee S. H., Kasaeian A., Kedir M. S., Khader Y. S., Khang Y. H., Kim D., Leigh J., Linn S., Lunevicius R., El Razek H. M. A., Malekzadeh R., Malta D. C., Marcenes W., Markos D., Melaku Y. A., Meles K. G., Mendoza W., Mengiste D. T., Meretoja T. J., Miller T. R., Mohammad K. A., Mohammadi A., Mohammed S., Moradi-Lakeh M., Nagel G., Nand D., Le Nguyen Q., Nolte S., Ogbo F. A., Oladimeji K. E., Oren E., Pa M., Park E. K., Pereira D. M., Plass D., Qorbani M., Radfar A., Rafay A., Rahman M., Rana S. M., Soreide K., Satpathy M., Sawhney M., Sepanlou S. G., Shaikh M. A., She J., Shiue I., Shore H. R., Shrime M. G., So S., Soneji S., Stathopoulou V., Stroumpoulis K., Sufiyan M. B., Sykes B. L., Tabares-Seisdedos R., Tadese F., Tedla B. A., Tessema G. A., Thakur J. S., Tran B. X., Ukwaja K. N., Uzochukwu B. S. C., Vlassov V. V., Weiderpass E., Wubshet Terefe M., Yebyo H. G., Yimam H. H., Yonemoto N., Younis M. Z., Yu C., Zaidi Z., Zaki M. E. S., Zenebe Z. M., Murray C. J. L., Naghavi M.: Global, regional, and national cancer incidence, mortality, years of life lost, years lived with disability, and disability-adjusted life-years for 32 cancer groups, 1990 to 2015: A systematic analysis for the global burden of disease study. JAMA Oncol 2017, 3(4):524-548.
6.Warnakulasuriya S.: Global epidemiology of oral and oropharyngeal cancer. Oral Oncol 2009, 45(4-5):309-316.
7.Petersen P. E.: Oral cancer prevention and control--the approach of the world health organization. Oral Oncol 2009, 45(4-5):454-460.
8.Cancer registry annual report. Taiwan: Health Promoyion Admnistration, Ministry of Health and Welfare, 2014. Available from: https://www.hpa.gov.tw/File/Attach/7330/File_6792.pdf
9.Ko Y. C., Huang Y. L., Lee C. H., Chen M. J., Lin L. M., Tsai C. C.: Betel quid chewing, cigarette smoking and alcohol consumption related to oral cancer in Taiwan. J Oral Pathol Med 1995, 24(10):450-453.
10.Myoung H., Hong S. P., Yun P. Y., Lee J. H., Kim M. J.: Anti-cancer effect of genistein in oral squamous cell carcinoma with respect to angiogenesis and in vitro invasion. Cancer Sci 2003, 94(2):215-220.
11.Krishna Rao S. V., Mejia G., Roberts-Thomson K., Logan R.: Epidemiology of oral cancer in Asia in the past decade--an update (2000-2012). Asian Pac J Cancer Prev 2013, 14(10):5567-5577.
12.Day G. L., Blot W. J.: Second primary tumors in patients with oral cancer. Cancer-am Cancer Soc 1992, 70(1):14-19.
13.Petti S., Masood M., Scully C.: The magnitude of tobacco smoking-betel quid chewing-alcohol drinking interaction effect on oral cancer in South-East Asia. A meta-analysis of observational studies. PLoS One 2013, 8(11):e78999.
14.Valavanidis A., Vlachogianni T., Fiotakis K.: Tobacco smoke: Involvement of reactive oxygen species and stable free radicals in mechanisms of oxidative damage, carcinogenesis and synergistic effects with other respirable particles. Int J Env Res Pub He 2009, 6(2):445-462.
15.Harris E. L.: Association of oral cancers with alcohol consumption: Exploring mechanisms. Jnci-J Natl Cancer I 1997, 89(22):1656-1657.
16.Lee H. C., Yin P. H., Yu T. N., Chang Y. D., Hsu W. C., Kao S. Y., Chi C. W., Liu T. Y., Wei Y. H.: Accumulation of mitochondrial DNA deletions in human oral tissues -- effects of betel quid chewing and oral cancer. Mutat Res-Gen Tox En 2001, 493(1-2):67-74.
17.Wong D. T., Gallagher G. T., Gertz R., Chang A. L., Shklar G.: Transforming growth factor alpha in chemically transformed hamster oral keratinocytes. Cancer Res 1988, 48(11):3130-3134.
18.Todd R., Chou M. Y., Matossian K., Gallagher G. T., Donoff R. B., Wong D. T.: Cellular sources of transforming growth factor-alpha in human oral cancer. J Dent Res 1991, 70(5):917-923.
19.Grandis J. R., Tweardy D. J.: Elevated levels of transforming growth factor alpha and epidermal growth factor receptor messenger RNA are early markers of carcinogenesis in head and neck cancer. Cancer Res 1993, 53(15):3579-3584.
20.Todd R., Donoff R. B., Wong D. T.: The molecular biology of oral carcinogenesis: Toward a tumor progression model. J Oral Maxil Surg 1997, 55(6):613-623.
21.Spandidos D. A., Lamothe A., Field J. K.: Multiple transcriptional activation of cellular oncogenes in human head and neck solid tumours. Anticancer Res 1985, 5(2):221-224.
22.Callender T., el-Naggar A. K., Lee M. S., Frankenthaler R., Luna M. A., Batsakis J. G.: PRAD-1 (CCND1)/cyclin D1 oncogene amplification in primary head and neck squamous cell carcinoma. Cancer 1994, 74(1):152-158.
23.Hooper M. L.: The role of the p53 and Rb-1 genes in cancer, development and apoptosis. J Cell Sci Suppl 1994, 18:13-17.
24.Le Campion A. C. O. V., Ribeiro C. M. B., Luiz R. R., da Silva Junior F. F., Barros H. C. S., Dos Santos K. C. B., Ferreira S. J., Goncalves L. S., Ferreira S. M. S.: Low survival rates of oral and oropharyngeal squamous cell carcinoma. Int J Dent 2017, 2017:5815493.
25.Roing M., Hirsch J. M., Holmstrom I., Schuster M.: Making new meanings of being in the world after treatment for oral cancer. Qual Health Res 2009, 19(8):1076-1086.
26.Vanneman M., Dranoff G.: Combining immunotherapy and targeted therapies in cancer treatment. Nat Rev Cancer 2012, 12(4):237-251.
27.Tolentino Ede S., Centurion B. S., Ferreira L. H., Souza A. P., Damante J. H., Rubira-Bullen I. R.: Oral adverse effects of head and neck radiotherapy: Literature review and suggestion of a clinical oral care guideline for irradiated patients. J Appl Oral Sci 2011, 19(5):448-454.
28.Price K. A., Cohen E. E.: Current treatment options for metastatic head and neck cancer. Curr Treat Options Oncol 2012, 13(1):35-46.
29.Andreadis C., Vahtsevanos K., Sidiras T., Thomaidis I., Antoniadis K., Mouratidou D.: 5-Fluorouracil and cisplatin in the treatment of advanced oral cancer. Oral Oncol 2003, 39(4):380-385.
30.Chang P. H., Wang C. H., Huang J. S., Lai C. H., Wu T. H., Lan Y. J., Tsai J. C., Chen E. Y., Yang S. W., Yeh K. Y.: Low body mass index at 3 months following adjuvant chemoradiation affects survival of postoperative locally advanced oral cavity cancer patients. Laryngoscope 2012, 122(10):2193-2198.
31.Stenson K. M., Kunnavakkam R., Cohen E. E., Portugal L. D., Blair E., Haraf D. J., Salama J., Vokes E. E.: Chemoradiation for patients with advanced oral cavity cancer. Laryngoscope 2010, 120(1):93-99.
32.Truong M. T., Zhang Q., Rosenthal D. I., List M., Axelrod R., Sherman E., Weber R., Nguyen-Tan P. F., El-Naggar A., Konski A., Galvin J., Schwartz D., Trotti A., Silverman C., Singh A., Godette K., Bonner J. A., Jones C. U., Garden A. S., Shenouda G., Matthiesen C., Le Q. T., Bruner D.: Quality of life and performance status from a substudy conducted within a prospective phase 3 randomized trial of concurrent accelerated radiation plus cisplatin with or without cetuximab for locally advanced head and neck carcinoma: Nrg oncology radiation therapy oncology group 0522. Int J Radiat Oncol Biol Phys 2017, 97(4):687-699.
33.Harrington K., Ferris R. L., Shaw J., Taylor F., Derosa M., Turner-Bowker D., Morrissey L., Cocks K., Kiyota N., Gillison M., Guigay J.: Head and neck cancer patient-reported outcomes (PROs) in recurrent or metastatic (R/M) squamous cell carcinoma of the head and neck (SCCHN) treated with nivolumab (nivo) or investigator’s choice (IC): CheckMate 141. Ann Oncol 2016, 27(suppl_6):552-587.
34.Doudna J. A., Charpentier E.: Genome editing. The new frontier of genome engineering with CRISPR-Cas9. Science 2014, 346(6213):1258096.
35.Gaudelli N. M., Komor A. C., Rees H. A., Packer M. S., Badran A. H., Bryson D. I., Liu D. R.: Programmable base editing of A•T to G•C in genomic DNA without DNA cleavage. Nature 2017, 551:464-471.
36.Kumar M. S., Masthan K. M., Babu N. A., Dash K. C.: Gene therapy in oral cancer: A review. J Clin Diagn Res 2013, 7(6):1261-1263.
37.Lo Conte M., Lin J., Wilson M. A., Carroll K. S.: A chemical approach for the detection of protein sulfinylation. ACS Chem Biol 2015, 10(8):1825-1830.
38.Manda G., Isvoranu G., Comanescu M. V., Manea A., Debelec Butuner B., Korkmaz K. S.: The redox biology network in cancer pathophysiology and therapeutics. Redox Biol 2015, 5:347-357.
39.Kalyanaraman B., Cheng G., Hardy M., Ouari O., Bennett B., Zielonka J.: Teaching the basics of reactive oxygen species and their relevance to cancer biology: Mitochondrial reactive oxygen species detection, redox signaling, and targeted therapies. Redox Biol 2018, 15:347-362.
40.Safe S., Kasiappan R.: Natural products as mechanism-based anticancer agents: Sp transcription factors as targets. Phytother Res 2016, 30(11):1723-1732.
41.Kesarwala A. H., Krishna M. C., Mitchell J. B.: Oxidative stress in oral diseases. Oral Dis 2016, 22(1):9-18.
42.Gorrini C., Harris I. S., Mak T. W.: Modulation of oxidative stress as an anticancer strategy. Nat Rev Drug Discov 2013, 12(12):931-947.
43.Schumacker P. T.: Reactive oxygen species in cancer: A dance with the devil. Cancer Cell 2015, 27(2):156-157.
44.Barrera G.: Oxidative stress and lipid peroxidation products in cancer progression and therapy. ISRN Oncol 2012, 2012:137289.
45.Sullivan L. B., Chandel N. S.: Mitochondrial reactive oxygen species and cancer. Cancer Metab 2014, 2:17.
46.Galadari S., Rahman A., Pallichankandy S., Thayyullathil F.: Reactive oxygen species and cancer paradox: To promote or to suppress? Free Radic Biol Med 2017, 104:144-164.
47.Choi Inpyo: Reactive oxygen species and cancer. Hanyang Med Rev 2013, 33(2):118-122.
48.Poljsak B., Suput D., Milisav I.: Achieving the balance between ROS and antioxidants: When to use the synthetic antioxidants. Oxid Med Cell Longev 2013, 2013:956792.
49.Trachootham D., Alexandre J., Huang P.: Targeting cancer cells by ROS-mediated mechanisms: A radical therapeutic approach? Nat Rev Drug Discov 2009, 8(7):579-591.
50.Newman D. J., Cragg G. M.: Natural products as sources of new drugs over the 30 years from 1981 to 2010. J Nat Prod 2012, 75(3):311-335.
51.Orlikova B., Legrand N., Panning J., Dicato M., Diederich M.: Anti-inflammatory and anticancer drugs from nature. Cancer Treat Res 2014, 159:123-143.
52.Bernardini S., Tiezzi A., Laghezza Masci V., Ovidi E.: Natural products for human health: An historical overview of the drug discovery approaches. Nat Prod Res 2017:1-25.
53.Kobayashi J.: Search for new bioactive marine natural products and application to drug development. Chem pharm bull 2016, 64(8):1079-1083.
54.Malve H.: Exploring the ocean for new drug developments: Marine pharmacology. J Pharm Bioallied Sci 2016, 8(2):83-91.
55.Wu S. Y., Sung P. J., Chang Y. L., Pan S. L., Teng C. M.: Heteronemin, a spongean sesterterpene, induces cell apoptosis and autophagy in human renal carcinoma cells. Biomed Res Int 2015, 2015:738241.
56.Gerwick W. H., Moore B. S.: Lessons from the past and charting the future of marine natural products drug discovery and chemical biology. Chem Biol 2012, 19(1):85-98.
57.Schumacher M., Kelkel M., Dicato M., Diederich M.: Gold from the sea: Marine compounds as inhibitors of the hallmarks of cancer. Biotechnol Adv 2011, 29(5):531-547.
58.Lee J. C., Hou M. F., Huang H. W., Chang F. R., Yeh C. C., Tang J. Y., Chang H. W.: Marine algal natural products with anti-oxidative, anti-inflammatory, and anti-cancer properties. Cancer Cell Int 2013, 13(1):55.
59.Mayer A. M., Glaser K. B., Cuevas C., Jacobs R. S., Kem W., Little R. D., McIntosh J. M., Newman D. J., Potts B. C., Shuster D. E.: The odyssey of marine pharmaceuticals: A current pipeline perspective. Trends Pharmacol Sci 2010, 31(6):255-265.
60.Mayer A. M., Rodriguez A. D., Taglialatela-Scafati O., Fusetani N.: Marine pharmacology in 2009-2011: Marine compounds with antibacterial, antidiabetic, antifungal, anti-inflammatory, antiprotozoal, antituberculosis, and antiviral activities; affecting the immune and nervous systems, and other miscellaneous mechanisms of action. Mar Drugs 2013, 11(7):2510-2573.
61.Mayer A. M., Nguyen M., Newman D. J., Glaser K. B.: The marine pharmacology and pharmaceuticals pipeline in 2015. Faseb J 2016, 30(1 Supplement):932-937.
62.Farooqi A. A., Fayyaz S., Hou M. F., Li K. T., Tang J. Y., Chang H. W.: Reactive oxygen species and autophagy modulation in non-marine drugs and marine drugs. Mar Drugs 2014, 12(11):5408-5424.
63.Farooqi A. A., Li K. T., Fayyaz S., Chang Y. T., Ismail M., Liaw C. C., Yuan S. S., Tang J. Y., Chang H. W.: Anticancer drugs for the modulation of endoplasmic reticulum stress and oxidative stress. Tumour Biol 2015, 36(8):5743-5752.
64.Yeh C. C., Yang J. I., Lee J. C., Tseng C. N., Chan Y. C., Hseu Y. C., Tang J. Y., Chuang L. Y., Huang H. W., Chang F. R., Chang H. W.: Anti-proliferative effect of methanolic extract of Gracilaria tenuistipitata on oral cancer cells involves apoptosis, DNA damage, and oxidative stress. Bmc Complem Altern M 2012, 12(1):142.
65.Yeh C. C., Tseng C. N., Yang J. I., Huang H. W., Fang Y., Tang J. Y., Chang F. R., Chang H. W.: Antiproliferation and induction of apoptosis in Ca9-22 oral cancer cells by ethanolic extract of Gracilaria tenuistipitata. Molecules 2012, 17(9):10916-10927.
66.Velatooru L. R., Baggu C. B., Janapala V. R.: Spatane diterpinoid from the brown algae, Stoechospermum marginatum induces apoptosis via ROS induced mitochondrial mediated caspase dependent pathway in murine B16F10 melanoma cells. Mol Carcinog 2016, 55(12):2222-2235.
67.Yang L., Wang P., Wang H., Li Q., Teng H., Liu Z., Yang W., Hou L., Zou X.: Fucoidan derived from Undaria pinnatifida induces apoptosis in human hepatocellular carcinoma SMMC-7721 cells via the ROS-mediated mitochondrial pathway. Mar Drugs 2013, 11(6):1961-1976.
68.Shih H. C., El-Shazly M., Juan Y. S., Chang C. Y., Su J. H., Chen Y. C., Shih S. P., Chen H. M., Wu Y. C., Lu M. C.: Cracking the cytotoxicity code: Apoptotic induction of 10-acetylirciformonin B is mediated through ROS generation and mitochondrial dysfunction. Mar Drugs 2014, 12(5):3072-3090.
69.Tang S. A., Zhou Q., Guo W. Z., Qiu Y., Wang R., Jin M., Zhang W., Li K., Yamori T., Dan S., Kong D.: In vitro antitumor activity of stellettin B, a triterpene from marine sponge Jaspis stellifera, on human glioblastoma cancer SF295 cells. Mar Drugs 2014, 12(7):4200-4213.
70.da Frota M. L., Jr., Braganhol E., Canedo A. D., Klamt F., Apel M. A., Mothes B., Lerner C., Battastini A. M., Henriques A. T., Moreira J. C.: Extracts of marine sponge Polymastia janeirensis induce oxidative cell death through a caspase-9 apoptotic pathway in human U138MG glioma cell line. Invest New Drugs 2009, 27(5):440-446.
71.Yen W. H., Hu L. C., Su J. H., Lu M. C., Twan W. H., Yang S. Y., Kuo Y. C., Weng C. F., Lee C. H., Kuo Y. H., Sung P. J.: Norcembranoidal diterpenes from a Formosan soft coral Sinularia sp. Molecules 2012, 17(12):14058-14066.
72.Lin Y. Y., Lin S. C., Feng C. W., Chen P. C., Su Y. D., Li C. M., Yang S. N., Jean Y. H., Sung P. J., Duh C. Y., Wen Z. H.: Anti-inflammatory and analgesic effects of the marine-derived compound excavatolide B isolated from the culture-type formosan gorgonian Briareum excavatum. Mar Drugs 2015, 13(5):2559-2579.
73.Ahmed A. F., Su J. H., Kuo Y. H., Sheu J. H.: Scabrolides E-G, three new norditerpenoids from the soft coral Sinularia scabra. J Nat Prod 2004, 67(12):2079-2082.
74.Ahmed A. F., Tai S. H., Wen Z. H., Su J. H., Wu Y. C., Hu W. P., Sheu J. H.: A C-3 methylated isocembranoid and 10-oxocembranoids from a formosan soft coral, Sinularia grandilobata. J Nat Prod 2008, 71(6):946-951.
75.Huang K. J., Chen Y. C., El-Shazly M., Du Y. C., Su J. H., Tsao C. W., Yen W. H., Chang W. B., Su Y. D., Yeh Y. T., Lu M. C.: 5-Episinuleptolide acetate, a norcembranoidal diterpene from the formosan soft coral Sinularia sp., induces leukemia cell apoptosis through Hsp90 inhibition. Molecules 2013, 18(3):2924-2933.
76.Hu L. C., Su J. H., Chiang M. Y., Lu M. C., Hwang T. L., Chen Y. H., Hu W. P., Lin N. C., Wang W. H., Fang L. S., Kuo Y. H., Sung P. J.: Flexibilins A-C, new cembrane-type diterpenoids from the Formosan soft coral, Sinularia flexibilis. Mar Drugs 2013, 11(6):1999-2012.
77.Jiang C. S., Li Y., Han G. Y., Guo Y. W.: Further casbane-type diterpenes from the soft coral Sinularia depressa. Chin J Nat Medicines 2014, 12(11):853-856.
78.Cooper E. L., Hirabayashi K., Strychar K. B., Sammarco P. W.: Corals and their potential applications to integrative medicine. Evid Based Complement Alternat Med 2014, 2014:184959.
79.Chen C. Y., Yen C. Y., Wang H. R., Yang H. P., Tang J. Y., Huang H. W., Hsu S. H., Chang H. W.: Tenuifolide B from cinnamomum tenuifolium stem selectively inhibits proliferation of oral cancer cells via apoptosis, ROS generation, mitochondrial depolarization, and DNA damage. Toxins 2016, 8(11):319.
80.Chiu C. C., Haung J. W., Chang F. R., Huang K. J., Huang H. M., Huang H. W., Chou C. K., Wu Y. C., Chang H. W.: Golden berry-derived 4beta-hydroxywithanolide E for selectively killing oral cancer cells by generating ROS, DNA damage, and apoptotic pathways. PLoS One 2013, 8(5):e64739.
81.Shoji N., Umeyama A., Arihara S.: A novel norditerpenoid from the okinawan soft coral Sinularia sp. J Nat Prod 1993, 56(9):1651-1653.
82.Ahmed A. F., Shiue R. T., Wang G. H., Dai C. F., Kuo Y. H., Sheu J. H.: Five novel norcembranoids from Sinularia leptoclados and S. parva. Tetrahedron 2003, 59(37):7337-7344.
83.Tseng Y. J., Ahmed A. F., Dai C. F., Chiang M. Y., Sheu J. H.: Sinulochmodins A-C, three novel terpenoids from the soft coral Sinularia lochmodes. Org Lett 2005, 7(17):3813-3816.
84.Su T. R., Lin J. J., Chiu C. C., Chen J. Y., Su J. H., Cheng Z. J., Hwang W. I., Huang H. H., Wu Y. J.: Proteomic investigation of anti-tumor activities exerted by sinularin against A2058 melanoma cells. Electrophoresis 2012, 33(7):1139-1152.
85.Su J. H., Ahmed A. F., Sung P. J., Chao C. H., Kuo Y. H., Sheu J. H.: Manaarenolides A-I, diterpenoids from the soft coral Sinularia manaarensis. J Nat Prod 2006, 69(8):1134-1139.
86.San Miguel S. M., Opperman L. A., Allen E. P., Zielinski J. E., Svoboda K. K.: Antioxidant combinations protect oral fibroblasts against metal-induced toxicity. Arch Oral Biol 2013, 58(3):299-310.
87.Chiu C. C., Liu P. L., Huang K. J., Wang H. M., Chang K. F., Chou C. K., Chang F. R., Chong I. W., Fang K., Chen J. S., Chang H. W., Wu Y. C.: Goniothalamin inhibits growth of human lung cancer cells through DNA damage, apoptosis, and reduced migration ability. J Agric Food Chem 2011, 59(8):4288-4293.
88.Su C. C., Chen J. Y., Din Z. H., Su J. H., Yang Z. Y., Chen Y. J., Wang R. Y., Wu Y. J.: 13-acetoxysarcocrassolide induces apoptosis on human gastric carcinoma cells through mitochondria-related apoptotic pathways: p38/JNK activation and PI3K/AKT suppression. Mar Drugs 2014, 12(10):5295-5315.
89.O''Brien M. A., Moravec R. A., Riss T. L.: Poly (ADP-ribose) polymerase cleavage monitored in situ in apoptotic cells. Biotechniques 2001, 30(4):886-891.
90.Jain R., Rawat A., Verma B., Markiewski M. M., Weidanz J. A.: Antitumor activity of a monoclonal antibody targeting major histocompatibility complex class I-Her2 peptide complexes. J Natl Cancer Inst 2013, 105(3):202-218.
91.Hawkins O., Verma B., Lightfoot S., Jain R., Rawat A., McNair S., Caseltine S., Mojsilovic A., Gupta P., Neethling F., Almanza O., Dooley W., Hildebrand W., Weidanz J.: An HLA-presented fragment of macrophage migration inhibitory factor is a therapeutic target for invasive breast cancer. J Immunol 2011, 186(11):6607-6616.
92.Xin F., Jiang L., Liu X., Geng C., Wang W., Zhong L., Yang G., Chen M.: Bisphenol A induces oxidative stress-associated DNA damage in INS-1 cells. Mutat Res Genet Toxicol Environ Mutagen 2014, 769:29-33.
93.Chen B. H., Chang H. W., Huang H. M., Chong I. W., Chen J. S., Chen C. Y., Wang H. M.: (-)-Anonaine induces DNA damage and inhibits growth and migration of human lung carcinoma h1299 cells. J Agric Food Chem 2011, 59(6):2284-2290.
94.Collins A. R.: The comet assay for DNA damage and repair: Principles, applications, and limitations. Mol Biotechnol 2004, 26(3):249-261.
95.Yen C. Y., Hou M. F., Yang Z. W., Tang J. Y., Li K. T., Huang H. W., Huang Y. H., Lee S. Y., Fu T. F., Hsieh C. Y., Chen B. H., Chang H. W.: Concentration effects of grape seed extracts in anti-oral cancer cells involving differential apoptosis, oxidative stress, and DNA damage. Bmc Complem Altern M 2015, 15(1):94.
96.Mukhopadhyay P., Rajesh M., Yoshihiro K., Hasko G., Pacher P.: Simple quantitative detection of mitochondrial superoxide production in live cells. Biochem Bioph Res Co 2007, 358(1):203-208.
97.Kaufmann S. H., Lee S. H., Meng X. W., Loegering D. A., Kottke T. J., Henzing A. J., Ruchaud S., Samejima K., Earnshaw W. C.: Apoptosis-associated caspase activation assays. Methods 2008, 44(3):262-272.
98.Takaki H., Koganemaru R., Iwakawa Y., Higuchi R., Miyamoto T.: Inhibitory effect of norditerpenes on LPS-induced TNF-alpha production from the Okinawan soft coral, Sinularia sp. Biol Pharm Bull 2003, 26(3):380-382.
99.Tseng Y. J., Wang S. K., Duh C. Y.: Secosteroids and norcembranoids from the soft coral Sinularia nanolobata. Mar Drugs 2013, 11(9):3288-3296.
100.Liang C. H., Wang G. H., Chou T. H., Wang S. H., Lin R. J., Chan L. P., So E. C., Sheu J. H.: 5-epi-Sinuleptolide induces cell cycle arrest and apoptosis through tumor necrosis factor/mitochondria-mediated caspase signaling pathway in human skin cancer cells. Biochim Biophys Acta 2012, 1820(7):1149-1157.
101.Liang C. H., Wang G. H., Liaw C. C., Lee M. F., Wang S. H., Cheng D. L., Chou T. H.: Extracts from Cladiella australis, Clavularia viridis and Klyxum simplex (soft corals) are capable of inhibiting the growth of human oral squamous cell carcinoma cells. Mar Drugs 2008, 6(4):595-606.
102.Ding H., Han C., Guo D., Chin Y. W., Ding Y., Kinghorn A. D., D''Ambrosio S. M.: Selective induction of apoptosis of human oral cancer cell lines by avocado extracts via a ROS-mediated mechanism. Nutr Cancer 2009, 61(3):348-356.
103.Jeong J. C., Jang S. W., Kim T. H., Kwon C. H., Kim Y. K.: Mulberry fruit (Moris fructus) extracts induce human glioma cell death in vitro through ROS-dependent mitochondrial pathway and inhibits glioma tumor growth in vivo. Nutr Cancer 2010, 62(3):402-412.
104.Widodo N., Priyandoko D., Shah N., Wadhwa R., Kaul S. C.: Selective killing of cancer cells by Ashwagandha leaf extract and its component withanone involves ROS signaling. PLoS One 2010, 5(10):e13536.
105.Samhan-Arias A. K., Martin-Romero F. J., Gutierrez-Merino C.: Kaempferol blocks oxidative stress in cerebellar granule cells and reveals a key role for reactive oxygen species production at the plasma membrane in the commitment to apoptosis. Free Radic Biol Med 2004, 37(1):48-61.
106.Oh S. H., Lim S. C.: A rapid and transient ROS generation by cadmium triggers apoptosis via caspase-dependent pathway in HepG2 cells and this is inhibited through N-acetylcysteine-mediated catalase upregulation. Toxicol Appl Pharmacol 2006, 212(3):212-223.
107.Li J. J., Tang Q., Li Y., Hu B. R., Ming Z. Y., Fu Q., Qian J. Q., Xiang J. Z.: Role of oxidative stress in the apoptosis of hepatocellular carcinoma induced by combination of arsenic trioxide and ascorbic acid. Acta Pharmacol Sin 2006, 27(8):1078-1084.
108.Ehlers R. A., Hernandez A., Bloemendal L. S., Ethridge R. T., Farrow B., Evers B. M.: Mitochondrial DNA damage and altered membrane potential (delta psi) in pancreatic acinar cells induced by reactive oxygen species. Surgery 1999, 126(2):148-155.
109.Orrenius S. Mechanisms of oxidative cell damage. Pol G, Albano E, Dianzani MU, editors: Birkhauser Verlag, Basel Switzerland; 1993.
110.Fahrmann J. F., Hardman W. E.: Omega 3 fatty acids increase the chemo-sensitivity of B-CLL-derived cell lines EHEB and MEC-2 and of B-PLL-derived cell line JVM-2 to anti-cancer drugs doxorubicin, vincristine and fludarabine. Lipids Health Dis 2013, 12:36.
111.Denecker G., Vercammen D., Steemans M., Vanden Berghe T., Brouckaert G., Van Loo G., Zhivotovsky B., Fiers W., Grooten J., Declercq W., Vandenabeele P.: Death receptor-induced apoptotic and necrotic cell death: differential role of caspases and mitochondria. Cell Death Differ 2001, 8(8):829-840.
112.el Sayed K. A., Hamann M. T.: A new norcembranoid dimer from the red sea soft coral Sinularia gardineri. J Nat Prod 1996, 59(7):687-689.
113.Gibson K. R., Neilson I. L., Barrett F., Winterburn T. J., Sharma S., MacRury S. M., Megson I. L.: Evaluation of the antioxidant properties of N-acetylcysteine in human platelets: Prerequisite for bioconversion to glutathione for antioxidant and antiplatelet activity. J Cardiovasc Pharmacol 2009, 54(4):319-326.
114.Chang H. S., Tang J. Y., Yen C. Y., Huang H. W., Wu C. Y., Chung Y. A., Wang H. R., Chen I. S., Huang M. Y., Chang H. W.: Antiproliferation of Cryptocarya concinna-derived cryptocaryone against oral cancer cells involving apoptosis, oxidative stress, and DNA damage. BMC Complem Altern M 2016, 16(1):94.
115.Shu C. W., Chang H. T., Wu C. S., Chen C. H., Wu S., Chang H. W., Kuo S. Y., Fu E., Liu P. F., Hsieh Y. D.: Rela-mediated becn1 expression is required for reactive oxygen species-induced autophagy in oral cancer cells exposed to low-power laser irradiation. PLoS One 2016, 11(9):e0160586.
116.Wu C. H., Bai L. Y., Tsai M. H., Chu P. C., Chiu C. F., Chen M. Y., Chiu S. J., Chiang J. H., Weng J. R.: Pharmacological exploitation of the phenothiazine antipsychotics to develop novel antitumor agents-A drug repurposing strategy. Sci Rep 2016, 6:27540.
117.Hseu Y. C., Lee M. S., Wu C. R., Cho H. J., Lin K. Y., Lai G. H., Wang S. Y., Kuo Y. H., Kumar K. J., Yang H. L.: The chalcone flavokawain B induces G2/M cell-cycle arrest and apoptosis in human oral carcinoma HSC-3 cells through the intracellular ROS generation and downregulation of the Akt/p38 MAPK signaling pathway. J Agr Food Chem 2012, 60(9):2385-2397.
118.Aruoma O. I., Halliwell B., Hoey B. M., Butler J.: The antioxidant action of N-acetylcysteine: Its reaction with hydrogen peroxide, hydroxyl radical, superoxide, and hypochlorous acid. Free Radical Bio Med 1989, 6(6):593-597.
119.Atalay F., Odabasoglu F., Halici M., Cadirci E., Aydin O., Halici Z., Cakir A.: N-acetyl cysteine has both gastro-protective and anti-inflammatory effects in experimental rat models: Its gastro-protective effect is related to its in vivo and in vitro antioxidant properties. J Cell Biochem 2016, 117(2):308-319.
120.Lasram M. M., Lamine A. J., Dhouib I. B., Bouzid K., Annabi A., Belhadjhmida N., Ahmed M. B., El Fazaa S., Abdelmoula J., Gharbi N.: Antioxidant and anti-inflammatory effects of N-acetylcysteine against malathion-induced liver damages and immunotoxicity in rats. Life Sci 2014, 107(1-2):50-58.
121.Sadowska A. M., Manuel Y. Keenoy B., De Backer W. A.: Antioxidant and anti-inflammatory efficacy of NAC in the treatment of COPD: Discordant in vitro and in vivo dose-effects: A review. Pulm Pharmacol Ther 2007, 20(1):9-22.
122.Mukhopadhyay P., Rajesh M., Hasko G., Hawkins B. J., Madesh M., Pacher P.: Simultaneous detection of apoptosis and mitochondrial superoxide production in live cells by flow cytometry and confocal microscopy. Nat Protoc 2007, 2(9):2295-2301.
123.Sena L. A., Chandel N. S.: Physiological roles of mitochondrial reactive oxygen species. Mol Cell 2012, 48(2):158-167.
124.Schaar C. E., Dues D. J., Spielbauer K. K., Machiela E., Cooper J. F., Senchuk M., Hekimi S., Van Raamsdonk J. M.: Mitochondrial and cytoplasmic ROS have opposing effects on lifespan. PLoS Genet 2015, 11(2):e1004972.
125.He Z., Simon H. U.: A novel link between p53 and ROS. Cell Cycle 2013, 12(2):201-202.
126.Imai Y., Ohnishi K., Yasumoto J., Kajiwara A., Yamakawa N., Takahashi A., Ohnishi T., Kirita T.: Glycerol enhances radiosensitivity in a human oral squamous cell carcinoma cell line (Ca9-22) bearing a mutant p53 gene via Bax-mediated induction of apoptosis. Oral Oncol 2005, 41(6):631-636.
127.Kaneda Y., Shimamoto H., Matsumura K., Arvind R., Zhang S., Sakai E., Omura K., Tsuchida N.: Role of caspase 8 as a determinant in chemosensitivity of p53-mutated head and neck squamous cell carcinoma cell lines. J Med Dent Sci 2006, 53(1):57-66.
128.Yasumoto J., Kirita T., Takahashi A., Ohnishi K., Imai Y., Yuki K., Ohnishi T.: Apoptosis-related gene expression after hyperthermia in human tongue squamous cell carcinoma cells harboring wild-type or mutated-type p53. Cancer Lett 2004, 204(1):41-51.
129.Ahmad T., Aggarwal K., Pattnaik B., Mukherjee S., Sethi T., Tiwari B. K., Kumar M., Micheal A., Mabalirajan U., Ghosh B., Sinha Roy S., Agrawal A.: Computational classification of mitochondrial shapes reflects stress and redox state. Cell Death Dis 2013, 4:e461.
130.Kim J. K., Kang K. A., Ryu Y. S., Piao M. J., Han X., Oh M. C., Boo S. J., Jeong S. U., Jeong Y. J., Chae S., Na S. Y., Hyun J. W.: Induction of endoplasmic reticulum stress via reactive oxygen species mediated by luteolin in melanoma cells. Anticancer Res 2016, 36(5):2281-2289.
131.Zafarullah M., Li W. Q., Sylvester J., Ahmad M.: Molecular mechanisms of N-acetylcysteine actions. Cell Mol Life Sci 2003, 60(1):6-20.
132.Neoh C. A., Wang R. Y., Din Z. H., Su J. H., Chen Y. K., Tsai F. J., Weng S. H., Wu Y. J.: Induction of apoptosis by sinulariolide from soft coral through mitochondrial-related and p38MAPK pathways on human bladder carcinoma cells. Mar Drugs 2012, 10(12):2893-2911.
133.Li H. H., Su J. H., Chiu C. C., Lin J. J., Yang Z. Y., Hwang W. I., Chen Y. K., Lo Y. H., Wu Y. J.: Proteomic investigation of the sinulariolide-treated melanoma cells A375: Effects on the cell apoptosis through mitochondrial-related pathway and activation of caspase cascade. Mar Drugs 2013, 11(7):2625-2642.
134.Chen Y. J., Su J. H., Tsao C. Y., Hung C. T., Chao H. H., Lin J. J., Liao M. H., Yang Z. Y., Huang H. H., Tsai F. J., Weng S. H., Wu Y. J.: Sinulariolide induced hepatocellular carcinoma apoptosis through activation of mitochondrial-related apoptotic and PERK/eIF2alpha/ATF4/CHOP pathway. Molecules 2013, 18(9):10146-10161.
135.Weinheimer A. J., Matson J. A., Hossain M. B., van der Helm D.: Marine anticancer agents: Sinularin and dihydrosinularin, new cembranolides from the soft coral, Sinularia flexibilis. Tetrahedron Lett 1977, 18(34):2923-2926.
136.Chan W. H., Shiao N. H., Lu P. Z.: CdSe quantum dots induce apoptosis in human neuroblastoma cells via mitochondrial-dependent pathways and inhibition of survival signals. Toxicol Lett 2006, 167(3):191-200.
137.Shieh J. M., Shen C. J., Chang W. C., Cheng H. C., Chan Y. Y., Huang W. C., Chang W. C., Chen B. K.: An increase in reactive oxygen species by deregulation of ARNT enhances chemotherapeutic drug-induced cancer cell death. PLoS One 2014, 9(6):e99242.
138.Hung J. H., Chen C. Y., Omar H. A., Huang K. Y., Tsao C. C., Chiu C. C., Chen Y. L., Chen P. H., Teng Y. N.: Reactive oxygen species mediate terbufos-induced apoptosis in mouse testicular cell lines via the modulation of cell cycle and pro-apoptotic proteins. Environ Toxicol 2016, 31(12):1888-1898.
139.Lien J. C., Lin M. W., Chang S. J., Lai K. C., Huang A. C., Yu F. S., Chung J. G.: Tetrandrine induces programmed cell death in human oral cancer CAL 27 cells through the reactive oxygen species production and caspase-dependent pathways and associated with beclin-1-induced cell autophagy. Environ Toxicol 2017, 32(1):329-343.
140.Stark G. R., Taylor W. R. Analyzing the G2/M Checkpoint. In: Schönthal AH, editor. Checkpoint controls and cancer: Volume 1: Reviews and model systems. Totowa, NJ: Humana Press; 2004. p. 51-82.
141.Wu Y. J., Wong B. S., Yea S. H., Lu C. I., Weng S. H.: Sinularin induces apoptosis through mitochondria dysfunction and inactivation of the pI3K/Akt/mTOR pathway in gastric carcinoma cells. Mar Drugs 2016, 14(8):142.
142.Kastan M. B., Bartek J.: Cell-cycle checkpoints and cancer. Nature 2004, 432(7015):316-323.
143.He L., Nan M. H., Oh H. C., Kim Y. H., Jang J. H., Erikson R. L., Ahn J. S., Kim B. Y.: Asperlin induces G2/M arrest through ROS generation and ATM pathway in human cervical carcinoma cells. Biochem Bioph Res Co 2011, 409(3):489-493.
144.Kang N., Jian J. F., Cao S. J., Zhang Q., Mao Y. W., Huang Y. Y., Peng Y. F., Qiu F., Gao X. M.: Physalin A induces G2/M phase cell cycle arrest in human non-small cell lung cancer cells: Involvement of the p38 MAPK/ROS pathway. Mol Cell Biochem 2016, 415(1-2):145-155.
145.Hua K. F., Liao P. C., Fang Z., Yang F. L., Yang Y. L., Chen Y. L., Chiu Y. C., Liu M. L., Lam Y., Wu S. H.: Generation of reactive oxygen species by polyenylpyrroles derivatives causes DNA damage leading to G2/M arrest and apoptosis in human oral squamous cell carcinoma cells. PLoS One 2013, 8(6):e67603.
146.Nicolini F., Burmistrova O., Marrero M. T., Torres F., Hernandez C., Quintana J., Estevez F.: Induction of G2/M phase arrest and apoptosis by the flavonoid tamarixetin on human leukemia cells. Mol Carcinog 2014, 53(12):939-950.
147.Wang H., Zhang T., Sun W., Wang Z., Zuo D., Zhou Z., Li S., Xu J., Yin F., Hua Y., Cai Z.: Erianin induces G2/M-phase arrest, apoptosis, and autophagy via the ROS/JNK signaling pathway in human osteosarcoma cells in vitro and in vivo. Cell Death Dis 2016, 7(6):e2247.
148.Fang C., Zhang J., Qi D., Fan X., Luo J., Liu L., Tan Q.: Evodiamine induces G2/M arrest and apoptosis via mitochondrial and endoplasmic reticulum pathways in H446 and H1688 human small-cell lung cancer cells. PLoS One 2014, 9(12):e115204.
149.Rao P. C., Begum S., Jahromi M. A., Jahromi Z. H., Sriram S., Sahai M.: Cytotoxicity of withasteroids: Withametelin induces cell cycle arrest at G2/M phase and mitochondria-mediated apoptosis in non-small cell lung cancer A549 cells. Tumour Biol 2016, 37(9):12579-12587.
150.Carpi S., Fogli S., Romanini A., Pellegrino M., Adinolfi B., Podesta A., Costa B., Da Pozzo E., Martini C., Breschi M. C., Nieri P.: AM251 induces apoptosis and G2/M cell cycle arrest in A375 human melanoma cells. Anti-cancer Drug 2015, 26(7):754-762.
151.Kello M., Drutovic D., Pilatova M. B., Tischlerova V., Perjesi P., Mojzis J.: Chalcone derivatives cause accumulation of colon cancer cells in the G2/M phase and induce apoptosis. Life Sci 2016, 150:32-38.
152.Panieri E., Santoro M. M.: ROS homeostasis and metabolism: a dangerous liason in cancer cells. Cell Death Dis 2016, 7(6):e2253.
153.Lambeth J. D.: NOX enzymes and the biology of reactive oxygen. Nat Rev Immunol 2004, 4(3):181-189.
154.Fattorusso E., Luciano P., Putra M., Taglialatela-Scafati O., Ianaro A., Panza E., Bavestrello G., Cerrano C.: Chloroscabrolides, chlorinated norcembranoids from the Indonesian soft coral Sinularia sp. Tetrahedron 2011, 67(41):7983-7988.
155.Wu Y., Wang D., Gao Y., Feng J., Zhang X.: New α-methylene-γ-butyrolactone derivatives as potential fungicidal agents: Design, synthesis and antifungal activities. Molecules 2016, 21(2):130.
156.Gach K., Janecka A.: α-methylene-γ-lactones as a novel class of anti-leukemic agents. Anti-Cancer Agent Me 2014, 14(5):688-694.
157.Molnar J., Szebeni G. J., Csupor-Loffler B., Hajdu Z., Szekeres T., Saiko P., Ocsovszki I., Puskas L. G., Hohmann J., Zupko I.: Investigation of the antiproliferative properties of natural sesquiterpenes from Artemisia asiatica and Onopordum acanthium on HL-60 cells in vitro. Int J Mol Sci 2016, 17(2):83.
158.Czyz M., Lesiak-Mieczkowska K., Koprowska K., Szulawska-Mroczek A., Wozniak M.: Cell context-dependent activities of parthenolide in primary and metastatic melanoma cells. Br J Pharmacol 2010, 160(5):1144-1157.
159.Kreuger M. R., Grootjans S., Biavatti M. W., Vandenabeele P., D''Herde K.: Sesquiterpene lactones as drugs with multiple targets in cancer treatment: focus on parthenolide. Anticancer Drugs 2012, 23(9):883-896.
160.Mathema V. B., Koh Y. S., Thakuri B. C., Sillanpaa M.: Parthenolide, a sesquiterpene lactone, expresses multiple anti-cancer and anti-inflammatory activities. Inflammation 2012, 35(2):560-565.
161.Zhang S., Won Y. K., Ong C. N., Shen H. M.: Anti-cancer potential of sesquiterpene lactones: bioactivity and molecular mechanisms. Curr Med Chem Anticancer Agents 2005, 5(3):239-249.
162.Kupchan S. M., Eakin M. A., Thomas A. M.: Tumor inhibitors. 69. Structure-cytotoxicity relationships among the sesquiterpene lactones. J Med Chem 1971, 14(12):1147-1152.
電子全文 電子全文(網際網路公開日期:20230116)
QRCODE
 
 
 
 
 
                                                                                                                                                                                                                                                                                                                                                                                                               
第一頁 上一頁 下一頁 最後一頁 top
系統版面圖檔 系統版面圖檔