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研究生(外文):Yong-Shiou Lin
論文名稱:海洋放線菌Streptomyces sp.萃取物Lu01-M之抗前列腺癌機制
論文名稱(外文):Anti-prostate cancer mechanism of Lu01-M extract from marine actinomycete, Streptomyces sp.
指導教授(外文):Mei-Chin Lu
口試委員(外文):Hsueh-Wei ChangYi-Chang LiuMei-Chin Lu
外文關鍵詞:marine natural productsmarine actinomycetesprostate cancer
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海洋天然物的物種來源有珊瑚、海綿、海鞘、軟體動物、藻及微生物等,這些化合物的生物活性可作為藥物開發來源,被視為治療疾病的重要支柱,但越來越多研究顯示,許多存在於海洋生物中的活性物質,事實上是由共生微生物 (包括細菌、真菌及藻類等)之間化學相互作用所產生,其中以海洋放線菌的二次代謝物被認為在海洋天然物來源貢獻上最為重要。本篇從海洋底泥沉積物篩選出海洋放線菌Streptomyces sp.,利用乙酸乙酯萃取分離出具抗前列腺癌效果的二次代謝物Lu01-M,結果發現,藥物處理對三株前列腺癌細胞之存活率隨著時間或濃度的增加而明顯下降,而以前列腺癌細胞PC3最為敏感,24小時的半抑制濃度 (IC50)為2.45±0.27 μg/mL,同時藥物也會影響癌細胞週期,以及抑制癌細胞增生與遷徙能力。Lu01-M隨著劑量提升會破壞粒線體膜電位,同時誘發活性氧化物與內質網壓力,並抑制p-Akt信號路徑,導致細胞存活率下降。動物實驗結果顯示,Lu01-M可抑制腫瘤生長,且不會對動物本身體重及生化指數造成影響。綜合以上,Lu01-M在抗癌藥物發展上極具有開發之潛力。
There are many sources of marine natural products, including corals, sponges, tunicates, mollusks, algae, and microorganisms. The biological activity of these marine lives can be used as a source of drug development. It is considered as an important pillar for the treatment of diseases, but more and more research shows that many of the active substances present in marine organisms are in fact produced by chemical interactions between symbiotic microorganisms such us bacteria, fungi, algae, etc. The secondary metabolites of marine actinomycetes are considered to be the most important contribution to drug development. This article screened the marine actinomycetes Streptomyces sp., by using ethyl acetate to extract the secondary metabolite, Lu01-M. Lu01-M has anti-prostate cancer effect and the most sensitive cancer cell line was PC3, with IC50 2.45±0.27 μg/mL after 24 hours treatment. Thus, PC3 cells were subjected to further investigation. Lu01-M also affecting cell cycle, inhibited cells proliferation and migration. The use of increasing doses of Lu01-M (0 to 6.25 μg/mL) increased the percentage of disruption of mitochondrial membrane potential, induced the reactive oxygen species and endoplasmic reticulum stress, and inhibited the p-Akt signaling, leading to decrease the cell viability. We further expanded our investigation to evaluate the antitumor effect of Lu01-M in vivo xenograft animal models. Animal experiments showed that Lu01-M could inhibit tumor growth without affecting the body weight of mice and biochemical index. Taken together, these findings suggest that Lu01-M has a great potential in the development of anti-cancer drugs.
第一章、緒論 1
第二章、文獻回顧 5
第三章、研究材料與方法 17
第四章、結果 33
第五章、結論與討論 69
1. 台灣衛生福利部國民健康署, 106年死因統計結果分析. 2018. p. 5.
2. Ruiz-Torres, V., et al., An updated review on marine anticancer compounds: the use of virtual screening for the discovery of small-molecule cancer drugs. Molecules, 2017. 22(7).
3. Blunt, J.W., et al., Marine natural products. Nat Prod Rep, 2014. 31(2): p. 160-258.
4. Kulbicki, M., et al., Global biogeography of reef fishes: a hierarchical quantitative delineation of regions. PLoS One, 2013. 8(12).
5. Mendola, D., Aquacultural production of bryostatin 1 and ecteinascidin 743. Drugs from the Sea, ed. N. Fusetani. 2000. pp 120-133.
6. Morita, M. , et al., Parallel lives of symbionts and hosts: chemical mutualism in marine animals. Natural Product Reports, 2018.
7. Valdiglesias, V., et al., Okadaic acid: more than a diarrheic toxin. Mar Drugs, 2013. 11(11): p. 4328-49.
8. Cuevas, C., et al., Synthesis of ecteinascidin ET-743 and phthalascidin Pt-650 from cyanosafracin B. Org Lett, 2000. 2(16): p. 2545-8.
9. Galluzzi, L., et al., Essential versus accessory aspects of cell death: recommendations of the NCCD 2015. Cell Death Differ, 2015. 22(1): p. 58-73.
10. Høyer-Hansen, M., et al., Control of macroautophagy by calcium, calmodulin-dependent kinase Kinase-beta, and Bcl-2. Molecular Cell, 2007. 25(2): p. 193-205.
11. Rock, K.L., et al., The inflammatory response to cell death. Annu Rev Pathol, 2008. 3: p. 99-126.
12. Ouyang, L., et al., Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif, 2012. 45(6): p. 487-98.
13. Yonekawa, T. , et al., Autophagy and cell death. Essays Biochem, 2013. 55: p. 105-17.
14. Galluzzi, L. , et al., Necroptosis: a specialized pathway of programmed necrosis. Cell, 2008. 135(7): p. 1161-3.
15. McBride, H.M., et al., Mitochondria: more than just a powerhouse. Curr Biol, 2006. 16(14): p. R551-60.
16. Mammucari, C., et al., Signaling pathways in mitochondrial dysfunction and aging. Mech Ageing Dev, 2010. 131(7-8): p. 536-43.
17. Berdy, J., Bioactive microbial metabolites. J Antibiot (Tokyo), 2005. 58(1): p. 1-26.
18. Zhang, G., et al., Advanced tools in marine natural drug discovery. Curr Opin Biotechnol, 2016. 42: p. 13-23.
19. Mishra, B.B., et al., Natural products: an evolving role in future drug discovery. Eur J Med Chem, 2011. 46(10): p. 4769-807.
20. Kawagishi, F., et al., Total synthesis of ecteinascidin 743. J Am Chem Soc, 2013. 135(37): p. 13684-7.
21. Ceballos, P.A., et al., Synthesis of ecteinascidin 743 analogues from cyanosafracin B: Isolation of a kinetically stable quinoneimine tautomer of a 5-hydroxyindole. European Journal of Organic Chemistry, 2006(8): p. 1926-1933.
22. Huang, J.-L., Characterization of marine natural products as anticancer agents, in Institute of Molecular Medicine and Bioengineering. 2012, National Chiao Tung University. p. 2.
23. Nielsen, J.C., et al., Development of fungal cell factories for the production of secondary metabolites: Linking genomics and metabolism. Synth Syst Biotechnol, 2017. 2(1): p. 5-12.
24. Bonugli-Santos, R.C., et al., Marine-derived fungi: diversity of enzymes and biotechnological applications. Front Microbiol, 2015. 6.
25. Selvakumar, J.N., et al., Bio prospecting of marine-derived streptomyces spectabilis VITJS10 and exploring its cytotoxicity against human liver cancer cell lines. Pharmacogn Mag, 2015. 11(Suppl 3): p. S469-73.
26. Haefner, B., Drugs from the deep: marine natural products as drug candidates. Drug Discov Today, 2003. 8(12): p. 536-44.
27. Blunt, J.W., et al., Marine natural products. Nat Prod Rep, 2018. 35(1): p. 8-53.
28. Nikapitiya, C., Bioactive secondary metabolites from marine microbes for drug discovery. Adv Food Nutr Res, 2012. 65: p. 363-87.
29. Mayer, A.M., et al., The odyssey of marine pharmaceuticals: a current pipeline perspective. Trends Pharmacol Sci, 2010. 31(6): p. 255-65.
30. Das, S., P.S. Lyla, et al., Distribution and generic composition of culturable marine actinomycetes from the sediments of Indian continental slope of Bay of Bengal. Chinese Journal of Oceanology and Limnology, 2008. 26(2): p. 166-177.
31. Bhatti, A.A., et al., Actinomycetes benefaction role in soil and plant health. Microb Pathog, 2017. 111: p. 458-467.
32. Deng, Y., et al., Recent advances in genetic modification systems for Actinobacteria. Appl Microbiol Biotechnol, 2017. 101(6): p. 2217-2226.
33. van der Meij, A., et al., Chemical ecology of antibiotic production by actinomycetes. FEMS Microbiology Reviews, 2017. 41(3): p. 392-416.
34. Ravikumar, S., et al., Anticancer property of sediment actinomycetes against MCF-7 and MDA-MB-231 cell lines. Asian Pac J Trop Biomed, 2012. 2(2): p. 92-6.
35. Kamjam, M., et al., Deep sea actinomycetes and their secondary metabolites. Front Microbiol, 2017. 8.
36. Manivasagan, P., et al., Pharmaceutically active secondary metabolites of marine actinobacteria. Microbiol Res, 2014. 169(4): p. 262-78.
37. Prabakarana, A.R.a.P., Actinomycetes and drug-an overview. American Journal of Drug Discovery and Development, 2011. 1: p. 75-84.
38. Raja, A., et al., Isolation and screening of psychrophilic actinomycetes from rothang hill soil against dental carries causative Streptococcus sp. Journal of Pure and Applied Microbiology, 2010. 4(1): p. 225-230.
39. Jemimah Naine.S, V.M.S.a.C.S.D., Novel anticancer compounds from marine actinomycetes : A Review. Journal of Pharmacy Research, 2011. 4: p. 1285-1287.
40. Anil K. Sharma, et al., Secondary metabolites derived from actinomycetes: iron modulation and their therapeutic potential. The Natural Products Journal, 2015.
41. Gulder, T.A.M., et al., Salinosporamide natural products: potent 20S proteasome inhibitors as promising cancer chemotherapeutics. Angew Chem Int Ed Engl, 2010. 49(49): p. 9346-67.
42. Diminic, J., et al., Evolutionary concepts in natural products discovery: what actinomycetes have taught us. J Ind Microbiol Biotechnol, 2014. 41(2): p. 211-7.
43. Subramani, R., et al., Marine actinomycetes: an ongoing source of novel bioactive metabolites. Microbiol Res, 2012. 167(10): p. 571-80.
44. Zhang, K., et al., Prostate cancer screening in Europe and Asia. Asian J Urol, 2017. 4(2): p. 86-95.
45. 台灣衛生福利部國民健康署, 105年死因結果統計分析. 2017. p. 19.
46. Gordetsky, J., et al., Grading of prostatic adenocarcinoma: current state and prognostic implications. Diagn Pathol, 2016. 11.
47. Kim, Y.S., et al., Apoptotic effect of demethoxyfumitremorgin C from marine fungus Aspergillus fumigatus on PC3 human prostate cancer cells. Chem Biol Interact, 2017. 269: p. 18-24.
48. Zustovich, F., et al., Therapeutic management of bone metastasis in prostate cancer: an update. Expert Review of Anticancer Therapy, 2016. 16(11): p. 1199-1211.
49. Caffo, O., et al., Clinical outcomes of castration-resistant prostate cancer treatments administered as third or fourth line following failure of docetaxel and other second-line treatment: results of an Italian multicentre study. Eur Urol, 2015. 68(1): p. 147-53.
50. Lee, J.C., et al., Auraptene induces apoptosis via myeloid cell leukemia 1-mediated activation of caspases in PC3 and DU145 prostate cancer cells. Phytotherapy Research, 2017. 31(6): p. 891-898.
51. Otto, T., et al., Cell cycle proteins as promising targets in cancer therapy. Nature Reviews Cancer, 2017. 17: p. 93.
52. Williams, et al., The cell cycle and cancer. J Pathol, 2012. 226(2): p. 352-64.
53. Barnum, et al., Cell cycle regulation by checkpoints. Methods Mol Biol, 2014. 1170: p. 29-40.
54. Malumbres, M., et al., Cell cycle, CDKs and cancer: a changing paradigm. Nature Reviews Cancer, 2009. 9: p. 153.
55. Lim, S., et al., Cdks, cyclins and CKIs: roles beyond cell cycle regulation. Development, 2013. 140(15): p. 3079.
56. Yam, C.H., et al., Cyclin A in cell cycle control and cancer. Cellular and Molecular Life Sciences CMLS, 2002. 59(8): p. 1317-1326.
57. Musgrove, E.A., et al., Cyclin D as a therapeutic target in cancer. Nature Reviews Cancer, 2011. 11: p. 558.
58. Lodish H, B.A., Zipursky SL, et al., Molecular cell biology. 4th edition. Overview of the Cell Cycle and Its Control. 2000, New York: W. H. Freeman.
59. Malumbres, M., Cyclin-dependent kinases. Genome Biol, 2014. 15(6): p. 122.
60. Vermeulen, K., et al., The cell cycle: a review of regulation, deregulation and therapeutic targets in cancer. Cell Prolif, 2003. 36(3): p. 131-49.
61. Lu, Z., et al., Ubiquitylation and proteasomal degradation of the p21(Cip1), p27(Kip1) and p57(Kip2) CDK inhibitors. Cell Cycle, 2010. 9(12): p. 2342-52.
62. Preyat, N., et al., Complex role of nicotinamide adenine dinucleotide in the regulation of programmed cell death pathways. Biochem Pharmacol, 2016. 101: p. 13-26.
63. Nikoletopoulou, V., et al., Crosstalk between apoptosis, necrosis and autophagy. Biochim Biophys Acta, 2013. 1833(12): p. 3448-3459.
64. Tseng, W.-Y., et al., TNFR signalling and its clinical implications. Cytokine, 2018. 101: p. 19-25.
65. Kearney, C.J., et al., An inflammatory perspective on necroptosis. Mol Cell, 2017. 65(6): p. 965-973.
66. Rowinsky, E.K., Targeted induction of apoptosis in cancer management: the emerging role of tumor necrosis factor-related apoptosis-inducing ligand receptor activating agents. J Clin Oncol, 2005. 23(36): p. 9394-407.
67. Elmore, S., Apoptosis: a review of programmed cell death. Toxicol Pathol, 2007. 35(4): p. 495-516.
68. Wang, X., et al., Necroptosis and neutrophil-associated disorders. Cell Death & Disease, 2018. 9(2): p. 111.
69. Hassan, M., et al., Apoptosis and molecular targeting therapy in cancer. Biomed Res Int, 2014. 2014.
70. Loreto, C., et al., The role of intrinsic pathway in apoptosis activation and progression in peyronie's disease. Biomed Res Int, 2014. 2014.
71. Caltabiano, R., et al., Apoptosis in temporomandibular joint disc with internal derangement involves mitochondrial-dependent pathways- an in vivo study. Acta Odontol Scand, 2013. 71(3-4): p. 577-83.
72. Fesik, S.W., Insights into programmed cell death through structural biology. Cell, 2000. 103(2): p. 273-82.
73. Loreto, C., et al., Apoptosis in displaced temporomandibular joint disc with and without reduction: an immunohistochemical study. J Oral Pathol Med, 2011. 40(1): p. 103-10.
74. Feng, Y., et al., The machinery of macroautophagy. Cell Research, 2013. 24: p. 24.
75. Goodall, M.L., et al., The autophagy machinery controls cell death switching between apoptosis and necroptosis. Dev Cell, 2016. 37(4): p. 337-349.
76. Klionsky, D.J., et al., A comprehensive glossary of autophagy-related molecules and processes (2nd edition). Autophagy, 2011. 7(11): p. 1273-94.
77. Kania, E., et al., Calcium homeostasis and ER stress in control of autophagy in cancer cells. Biomed Res Int, 2015. 2015.
78. Ávalos, Y., et al., Tumor suppression and promotion by autophagy. Biomed Res Int, 2014. 2014.
79. Thorburn, J., et al., Autophagy controls the kinetics and extent of mitochondrial apoptosis by regulating PUMA levels. Cell Rep, 2014. 7(1): p. 45-52.
80. Rabinowitz, et al., Autophagy and metabolism. Science, 2010. 330(6009): p. 1344-8.
81. Kuma, A., et al., Physiological role of autophagy as an intracellular recycling system: with an emphasis on nutrient metabolism. Semin Cell Dev Biol, 2010. 21(7): p. 683-90.
82. Sancak, Y., et al., The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science, 2008. 320(5882): p. 1496-501.
83. Galluzzi, L., et al., To die or not to die: that is the autophagic question. Curr Mol Med, 2008. 8(2): p. 78-91.
84. Shaw, R.J., et al., Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature, 2006. 441(7092): p. 424-30.
85. Gozuacik, D., et al., Autophagy as a cell death and tumor suppressor mechanism. Oncogene, 2004. 23(16): p. 2891-906.
86. Vaseva, A.V., et al., p53 opens the mitochondrial permeability transition pore to trigger necrosis. Cell, 2012. 149(7): p. 1536-48.
87. Cookson, B.T., et al., Pro-inflammatory programmed cell death. Trends Microbiol, 2001. 9(3): p. 113-4.
88. Gao, M., et al., Glutaminolysis and transferrin regulate ferroptosis. Mol Cell, 2015. 59(2): p. 298-308.
89. Degterev, A., et al., Chemical inhibitor of nonapoptotic cell death with therapeutic potential for ischemic brain injury. Nat Chem Biol, 2005. 1(2): p. 112-9.
90. Cho, Y.S., et al., Phosphorylation-driven assembly of the RIP1-RIP3 complex regulates programmed necrosis and virus-induced inflammation. Cell, 2009. 137(6): p. 1112-23.
91. Yuan, J., et al., Alternative cell death mechanisms in development and beyond. Genes Dev, 2010. 24(23): p. 2592-602.
92. Fulda, S., Repurposing anticancer drugs for targeting necroptosis. Cell Cycle, 2018: p. 1-4.
93. Foghsgaard, L., et al., Cathepsin B acts as a dominant execution protease in tumor cell apoptosis induced by tumor necrosis factor. The Journal of Cell Biology, 2001. 153(5): p. 999-1010.
94. Razaghi, A., et al., Negative regulators of cell death pathways in cancer: perspective on biomarkers and targeted therapies. Apoptosis, 2018. 23(2): p. 93-112.
95. Lalaoui, N., et al., Relevance of necroptosis in cancer. Immunol Cell Biol, 2017. 95(2): p. 137-145.
96. Ray, C.A., et al., The mode of death of pig kidney cells infected with cowpox virus is governed by the expression of the crmA gene. Virology, 1996. 217(1): p. 384-91.
97. Seo, J., et al., CHIP controls necroptosis through ubiquitylation- and lysosome-dependent degradation of RIPK3. Nature Cell Biology, 2016. 18(3): p. 291-+.
98. Lemke, J., et al., Getting TRAIL back on track for cancer therapy. Cell Death Differ, 2014. 21(9): p. 1350-64.
99. Osborn, S.L., et al., Fas-associated death domain (FADD) is a negative regulator of T-cell receptor-mediated necroptosis. Proc Natl Acad Sci U S A, 2010. 107(29): p. 13034-9.
100. Cabon, L., et al., AIF loss deregulates hematopoiesis and reveals different adaptive metabolic responses in bone marrow cells and thymocytes. Cell Death Differ, 2018. 25(5): p. 983-1001.
101. Alam, M.M., et al., A holistic view of cancer bioenergetics: mitochondrial function and respiration play fundamental roles in the development and progression of diverse tumors. Clin Transl Med, 2016. 5(1): p. 3.
102. Nunnari, J., et al., Mitochondria: in sickness and in health. Cell, 2012. 148(6): p. 1145-59.
103. Herst, P.M., et al., Functional mitochondria in health and disease. Front Endocrinol (Lausanne), 2017. 8.
104. Sebastian, D., et al., Mitochondrial dynamics: coupling mitochondrial fitness with healthy aging. Trends Mol Med, 2017. 23(3): p. 201-215.
105. Rivera, M., et al., Targeting multiple pro-apoptotic signaling pathways with curcumin in prostate cancer cells. PLoS One, 2017. 12(6): p. e0179587.
106. Trachootham, D., et al., Targeting cancer cells by ROS-mediated mechanisms: a radical therapeutic approach? Nature Reviews Drug Discovery, 2009. 8: p. 579.
107. Saito, T., et al., Molecular mechanisms of mitochondrial autophagy/mitophagy in the heart. Circulation Research, 2015. 116(8): p. 1477.
108. Chang, M.-C., et al., Induction of necrosis and apoptosis to KB cancer cells by sanguinarine is associated with reactive oxygen species production and mitochondrial membrane depolarization. Toxicology and Applied Pharmacology, 2007. 218(2): p. 143-151.
109. Papież, M.A., et al., Curcumin enhances the cytogenotoxic effect of etoposide in leukemia cells through induction of reactive oxygen species. Drug Des Devel Ther, 2016. 10: p. 557-70.
110. Santoro, V., et al., Role of reactive oxygen species in the abrogation of oxaliplatin activity by cetuximab in colorectal cancer. J Natl Cancer Inst, 2016. 108(6).
111. Nguyen, H.M., et al., Autophagy participates in the unfolded protein response in Toxoplasma gondii. FEMS Microbiol Lett, 2017. 364(15).
112. Zeeshan, H.M.A., et al., Endoplasmic reticulum stress and associated ROS. Int J Mol Sci, 2016. 17(3).
113. Niu, M., et al., Autophagy, endoplasmic reticulum stress and the unfolded protein response in intracerebral hemorrhage. Transl Neurosci, 2017. 8: p. 37-48.
114. Tse, G., et al., Reactive oxygen species, endoplasmic reticulum stress and mitochondrial dysfunction: the link with cardiac arrhythmogenesis. Front Physiol, 2016. 7.
115. Walter, P., et al., The unfolded protein response: from stress pathway to homeostatic regulation. Science, 2011. 334(6059): p. 1081-6.
116. Hoyer-Hansen, M., et al., Connecting endoplasmic reticulum stress to autophagy by unfolded protein response and calcium. Cell Death Differ, 2007. 14(9): p. 1576-82.
117. Schroder, M., et al., ER stress and the unfolded protein response. Mutat Res, 2005. 569(1-2): p. 29-63.
118. Zhao, L., et al., Endoplasmic reticulum stress in health and disease. Curr Opin Cell Biol, 2006. 18(4): p. 444-52.
119. Schindler, A.J., et al., In vitro reconstitution of ER-stress induced ATF6 transport in COPII vesicles. Proc Natl Acad Sci U S A, 2009. 106(42): p. 17775-80.
120. Marciniak, S.J., et al., CHOP induces death by promoting protein synthesis and oxidation in the stressed endoplasmic reticulum. Genes Dev, 2004. 18(24): p. 3066-77.
121. Tsaytler, P., et al., Selective inhibition of a regulatory subunit of protein phosphatase 1 restores proteostasis. Science, 2011. 332(6025): p. 91-4.
122. Sano, R., et al., ER stress-induced cell death mechanisms. Biochim Biophys Acta, 2013. 1833(12): p. 3460-3470.
123. Abdelmohsen, U.R., et al., Isolation, phylogenetic analysis and anti-infective activity screening of marine sponge-associated actinomycetes. Mar Drugs, 2010. 8(3): p. 399-412.
124. Jensen, P.R., et al., Culturable marine actinomycete diversity from tropical Pacific Ocean sediments. Environ Microbiol, 2005. 7(7): p. 1039-48.
125. Weber, A.M., et al., ATM and ATR as therapeutic targets in cancer. Pharmacology & Therapeutics, 2015. 149: p. 124-138.
126. Kerr, J.F., et al., Apoptosis: a basic biological phenomenon with wide-ranging implications in tissue kinetics. Br J Cancer, 1972. 26(4): p. 239-57.
127. Vermes, I., et al., A novel assay for apoptosis. Flow cytometric detection of phosphatidylserine expression on early apoptotic cells using fluorescein labelled Annexin V. J Immunol Methods, 1995. 184(1): p. 39-51.
128. Go, D.H., et al., 3-Decylcatechol induces autophagy-mediated cell death through the IRE1α/JNK/p62 in hepatocellular carcinoma cells. Oncotarget, 2017. 8(35): p. 58790-800.
129. Mizushima, N., et al., Methods in mammalian autophagy research. Cell, 2010. 140(3): p. 313-26.
130. Wang, X., The expanding role of mitochondria in apoptosis. Genes Dev, 2001. 15(22): p. 2922-33.
131. Liu, Y., et al., Generation of reactive oxygen species by the mitochondrial electron transport chain. J Neurochem, 2002. 80(5): p. 780-7.
132. Hamad, I., et al., Intracellular scavenging activity of Trolox (6-hydroxy-2,5,7,8-tetramethylchromane-2-carboxylic acid) in the fission yeast, Schizosaccharomyces pombe. J Nat Sci Biol Med, 2010. 1(1): p. 16-21.
133. Kim, E.J., et al., The beneficial effects of polyethylene glycol-superoxide dismutase on ovarian tissue culture and transplantation. J Assist Reprod Genet, 2015. 32(10): p. 1561-9.
134. Gu, S., et al., ROS-mediated endoplasmic reticulum stress and mitochondrial dysfunction underlie apoptosis induced by resveratrol and arsenic trioxide in A549 cells. Chem Biol Interact, 2016. 245: p. 100-9.
135. Das, T.P., et al., Inhibition of AKT promotes FOXO3a-dependent apoptosis in prostate cancer. Cell Death &Amp; Disease, 2016. 7: p. e2111.
136. Smith, J., et al., Chapter 3 - the ATM–Chk2 and ATR–Chk1 pathways in DNA damage signaling and cancer, in Advances in Cancer Research, G.F. Vande Woude and G. Klein, Editors. 2010, Academic Press. p. 73-112.
137. Bartek, J., et al., Chk1 and Chk2 kinases in checkpoint control and cancer. Cancer Cell, 2003. 3(5): p. 421-429.
138. Raynaud, C., et al., Chromatin meets the cell cycle. J Exp Bot, 2014. 65(10): p. 2677-89.
139. Sun, Y., et al., Programmed cell death and cancer. Postgrad Med J, 2009. 85(1001): p. 134-40.
140. Eliopoulos, et al., DNA damage response and autophagy: a meaningful partnership. Front Genet, 2016. 7.
141. Maiuri, M.C., et al., Self-eating and self-killing: crosstalk between autophagy and apoptosis. Nat Rev Mol Cell Biol, 2007. 8(9): p. 741-52.
142. Marino, G., et al., Self-consumption: the interplay of autophagy and apoptosis. Nat Rev Mol Cell Biol, 2014. 15(2): p. 81-94.
143. Lum, J.J., et al., Autophagy in metazoans: cell survival in the land of plenty. Nat Rev Mol Cell Biol, 2005. 6(6): p. 439-48.
144. Zhu, W., et al., Effect of PI3K/Akt signaling pathway on the process of prostate cancer metastasis to bone. Cell Biochem Biophys, 2015. 72(1): p. 171-7.
145. Galluzzi, L., et al., MLKL regulates necrotic plasma membrane permeabilization. Cell Res, 2014. 24(2): p. 139-40.
146. Ghanizadeh, A., et al., Targeting the mitochondrial electron transport chain in autism, a systematic review and synthesis of a novel therapeutic approach. Mitochondrion, 2013. 13(5): p. 515-9.
147. Trujillo, J., et al., Mitochondria as a target in the therapeutic properties of curcumin. Arch Pharm (Weinheim), 2014. 347(12): p. 873-84.
148. Yadav, N., et al.,Mitochondrial and postmitochondrial survival signaling in cancer. Mitochondrion, 2014. 16: p. 18-25.
149. Berridge, M.V., et al., Metabolic flexibility and cell hierarchy in metastatic cancer. Mitochondrion, 2010. 10(6): p. 584-8.
150. Lau, E., et al., PKCepsilon promotes oncogenic functions of ATF2 in the nucleus while blocking its apoptotic function at mitochondria. Cell, 2012. 148(3): p. 543-55.
151. Schieber, M., et al., ROS function in redox signaling and oxidative stress. Curr Biol, 2014. 24(10): p. R453-62.
152. Jiang, H.Y., et al., GCN2 phosphorylation of eIF2alpha activates NF-kappaB in response to UV irradiation. Biochem J, 2005. 385(Pt 2): p. 371-80.
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