Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

Yadav, N.; Kumar, S.; Marlowe, T.; Chaudhary, A. K.; Kumar, R.; Wang, J.; O'Malley, J.; Boland, P. M.; Jayanthi, S.; Kumar, T. K. S.; Yadava, N.; Chandra, D.

doi:10.1038/cddis.2015.305

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

Journal Article · Wed Nov 04 23:00:00 EST 2015 · Cell Death and Disease

DOI:https://doi.org/10.1038/cddis.2015.305· OSTI ID:1239287

Yadav, N. ^[1]; Kumar, S. ^[2]; Marlowe, T. ^[2]; Chaudhary, A. K. ^[2]; Kumar, R. ^[2]; Wang, J. ^[2]; O'Malley, J. ^[2]; Boland, P. M. ^[2]; Jayanthi, S. ^[3]; Kumar, T. K. S. ^[3]; Yadava, N. ^[4]; ^[2]

Roswell Park Cancer Institute, Buffalo, NY (United States); Department of Pharmacology and Therapeutics, Roswell Park Cancer Institute, Elm and Carlton Streets, Buffalo, NY 14263, USA
Roswell Park Cancer Institute, Buffalo, NY (United States)
Univ. of Arkansas, Fayetteville, AR (United States)
Pioneer Valley Life Sciences Inst., Springfield, MA (United States)

Cancer cells tend to develop resistance to various types of anticancer agents, whether they adopt similar or distinct mechanisms to evade cell death in response to a broad spectrum of cancer therapeutics is not fully defined. Current study concludes that DNA-damaging agents (etoposide and doxorubicin), ER stressor (thapsigargin), and histone deacetylase inhibitor (apicidin) target oxidative phosphorylation (OXPHOS) for apoptosis induction, whereas other anticancer agents including staurosporine, taxol, and sorafenib induce apoptosis in an OXPHOS-independent manner. DNA-damaging agents promoted mitochondrial biogenesis accompanied by increased accumulation of cellular and mitochondrial ROS, mitochondrial protein-folding machinery, and mitochondrial unfolded protein response. Induction of mitochondrial biogenesis occurred in a caspase activation-independent mechanism but was reduced by autophagy inhibition and p53-deficiency. Abrogation of complex-I blocked DNA-damage-induced caspase activation and apoptosis, whereas inhibition of complex-II or a combined deficiency of OXPHOS complexes I, III, IV, and V due to impaired mitochondrial protein synthesis did not modulate caspase activity. Mechanistic analysis revealed that inhibition of caspase activation in response to anticancer agents associates with decreased release of mitochondrial cytochrome c in complex-I-deficient cells compared with wild type (WT) cells. Gross OXPHOS deficiencies promoted increased release of apoptosis-inducing factor from mitochondria compared with WT or complex-I-deficient cells, suggesting that cells harboring defective OXPHOS trigger caspase-dependent as well as caspase-independent apoptosis in response to anticancer agents. Interestingly, DNA-damaging agent doxorubicin showed strong binding to mitochondria, which was disrupted by complex-I-deficiency but not by complex-II-deficiency. Thapsigargin-induced caspase activation was reduced upon abrogation of complex-I or gross OXPHOS deficiency whereas a reverse trend was observed with apicidin. Together, these finding provide a new strategy for differential mitochondrial targeting in cancer therapy.

View Accepted Manuscript (DOE)

Research Organization:: Roswell Park Cancer Institute, Buffalo, NY (United States)

Sponsoring Organization:: USDOE Office of Science (SC)

Grant/Contract Number:: FG02-01ER15161

OSTI ID:: 1239287

Journal Information:: Cell Death and Disease, Journal Name: Cell Death and Disease Journal Issue: 11 Vol. 6; ISSN 2041-4889

Publisher:: Nature Publishing GroupCopyright Statement

Country of Publication:: United States

Language:: English

References (63)

Loss of p53 causes mitochondrial DNA depletion and altered mitochondrial reactive oxygen species homeostasis Lebedeva, Maria A.; Eaton, Jana S.; Shadel, Gerald S. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1787, Issue 5 https://doi.org/10.1016/j.bbabio.2009.01.004	journal	May 2009
Genetic insights into OXPHOS defect and its role in cancer Chandra, Dhyan; Singh, Keshav K. Biochimica et Biophysica Acta (BBA) - Bioenergetics, Vol. 1807, Issue 6 https://doi.org/10.1016/j.bbabio.2010.10.023	journal	June 2011
Mitochondrial DNA mutations and breast tumorigenesis Yadav, Neelu; Chandra, Dhyan Biochimica et Biophysica Acta (BBA) - Reviews on Cancer, Vol. 1836, Issue 2 https://doi.org/10.1016/j.bbcan.2013.10.002	journal	December 2013
TZDs reduce mitochondrial ROS production and enhance mitochondrial biogenesis Fujisawa, Kazuo; Nishikawa, Takeshi; Kukidome, Daisuke Biochemical and Biophysical Research Communications, Vol. 379, Issue 1 https://doi.org/10.1016/j.bbrc.2008.11.141	journal	January 2009
Investigations of the potential effects of phosphorylation of the MWFE and ESSS subunits on complex I activity and assembly Yadava, N.; Potluri, P.; Scheffler, I. E. The International Journal of Biochemistry & Cell Biology, Vol. 40, Issue 3 https://doi.org/10.1016/j.biocel.2007.08.015	journal	January 2008
4E-BP Extends Lifespan upon Dietary Restriction by Enhancing Mitochondrial Activity in Drosophila Zid, Brian M.; Rogers, Aric N.; Katewa, Subhash D. Cell, Vol. 139, Issue 1 https://doi.org/10.1016/j.cell.2009.07.034	journal	October 2009
Hallmarks of Cancer: The Next Generation Hanahan, Douglas; Weinberg, Robert A. Cell, Vol. 144, Issue 5 https://doi.org/10.1016/j.cell.2011.02.013	journal	March 2011
Cardiolipin and the Nlrp3 Inflammasome O’Neill, Luke A. J. Cell Metabolism, Vol. 18, Issue 5 https://doi.org/10.1016/j.cmet.2013.10.013	journal	November 2013
Human OXR1 maintains mitochondrial DNA integrity and counteracts hydrogen peroxide-induced oxidative stress by regulating antioxidant pathways involving p21 Yang, Mingyi; Luna, Luisa; Sørbø, Jan Gunnar Free Radical Biology and Medicine, Vol. 77 https://doi.org/10.1016/j.freeradbiomed.2014.09.003	journal	December 2014
Dangerous Liaisons: Mitochondrial DNA Meets the NLRP3 Inflammasome Martinon, Fabio Immunity, Vol. 36, Issue 3 https://doi.org/10.1016/j.immuni.2012.03.005	journal	March 2012
Resveratrol depletes mitochondrial DNA and inhibition of autophagy enhances resveratrol-induced caspase activation Prabhu, Varun; Srivastava, Pragya; Yadav, Neelu Mitochondrion, Vol. 13, Issue 5 https://doi.org/10.1016/j.mito.2012.10.010	journal	September 2013
Mitochondrial and postmitochondrial survival signaling in cancer Yadav, Neelu; Chandra, Dhyan Mitochondrion, Vol. 16 https://doi.org/10.1016/j.mito.2013.11.005	journal	May 2014
Mitochondria: gatekeepers of response to chemotherapy Sarosiek, Kristopher A.; Ni Chonghaile, Triona; Letai, Anthony Trends in Cell Biology, Vol. 23, Issue 12 https://doi.org/10.1016/j.tcb.2013.08.003	journal	December 2013
Chinese hamster cell mutant with defective mitochondrial protein synthesis Ditta, G.; Soderberg, K.; Scheffler, I. E. Nature, Vol. 268, Issue 5615 https://doi.org/10.1038/268064a0	journal	July 1977
Human mitochondrial DNA deletions associated with mutations in the gene encoding Twinkle, a phage T7 gene 4-like protein localized in mitochondria Spelbrink, Johannes N.; Li, Fang-Yuan; Tiranti, Valeria Nature Genetics, Vol. 28, Issue 3 https://doi.org/10.1038/90058	journal	July 2001
Selective anticancer strategies via intervention of the death pathways relevant to cell transformation Li, Q-X; Yu, D. H.; Liu, G. Cell Death & Differentiation, Vol. 15, Issue 8 https://doi.org/10.1038/cdd.2008.48	journal	April 2008
Differential gene and transcript expression analysis of RNA-seq experiments with TopHat and Cufflinks Trapnell, Cole; Roberts, Adam; Goff, Loyal Nature Protocols, Vol. 7, Issue 3 https://doi.org/10.1038/nprot.2012.016	journal	March 2012
Mitochondria and cancer Wallace, Douglas C. Nature Reviews Cancer, Vol. 12, Issue 10 https://doi.org/10.1038/nrc3365	journal	September 2012
Mitochondrial DNA determines the cellular response to cancer therapeutic agents Singh, Keshav K.; Russell, James; Sigala, Barbara Oncogene, Vol. 18, Issue 48 https://doi.org/10.1038/sj.onc.1203056	journal	November 1999
Induction of regulatory T cells by macrophages is dependent on production of reactive oxygen species Kraaij, Marina D.; Savage, Nigel D. L.; van der Kooij, Sandra W. Proceedings of the National Academy of Sciences, Vol. 107, Issue 41 https://doi.org/10.1073/pnas.1012016107	journal	September 2010
Discrete mechanisms of mTOR and cell cycle regulation by AMPK agonists independent of AMPK Liu, X.; Chhipa, R. R.; Pooya, S. Proceedings of the National Academy of Sciences, Vol. 111, Issue 4 https://doi.org/10.1073/pnas.1311121111	journal	January 2014
The NDUFA1 gene product (MWFE protein) is essential for activity of complex I in mammalian mitochondria Au, H. C.; Seo, B. B.; Matsuno-Yagi, A. Proceedings of the National Academy of Sciences, Vol. 96, Issue 8 https://doi.org/10.1073/pnas.96.8.4354	journal	April 1999
Induction of a Caspase-3-like Activity by Calcium in Normal Cytosolic Extracts Triggers Nuclear Apoptosis in a Cell-free System Juin, Philippe; Pelletier, Maude; Oliver, Lisa Journal of Biological Chemistry, Vol. 273, Issue 28 https://doi.org/10.1074/jbc.273.28.17559	journal	July 1998
Mitochondrial Dysfunction Impairs Tumor Suppressor p53 Expression/Function Compton, Shannon; Kim, Chul; Griner, Nicholas B. Journal of Biological Chemistry, Vol. 286, Issue 23 https://doi.org/10.1074/jbc.m110.163063	journal	April 2011
Early Mitochondrial Activation and Cytochrome c Up-regulation during Apoptosis Chandra, Dhyan; Liu, Jun-Wei; Tang, Dean G. Journal of Biological Chemistry, Vol. 277, Issue 52 https://doi.org/10.1074/jbc.m207622200	journal	October 2002
Lipopolysaccharide Stimulates Mitochondrial Biogenesis via Activation of Nuclear Respiratory Factor-1 Suliman, Hagir B.; Carraway, Martha S.; Welty-Wolf, Karen E. Journal of Biological Chemistry, Vol. 278, Issue 42 https://doi.org/10.1074/jbc.m304719200	journal	August 2003
Mitochondrial reactive oxygen species promote production of proinflammatory cytokines and are elevated in TNFR1-associated periodic syndrome (TRAPS) Bulua, Ariel C.; Simon, Anna; Maddipati, Ravikanth The Journal of Experimental Medicine, Vol. 208, Issue 3 https://doi.org/10.1084/jem.20102049	journal	January 2011
Regulation of the Intrinsic Apoptosis Pathway by Reactive Oxygen Species Wu, Chu-Chiao; Bratton, Shawn B. Antioxidants & Redox Signaling, Vol. 19, Issue 6 https://doi.org/10.1089/ars.2012.4905	journal	August 2013
Composition and Dynamics of Human Mitochondrial Nucleoids Garrido, Nuria; Griparic, Lorena; Jokitalo, Eija Molecular Biology of the Cell, Vol. 14, Issue 4 https://doi.org/10.1091/mbc.e02-07-0399	journal	April 2003
Real time quantitative PCR. Heid, C. A.; Stevens, J.; Livak, K. J. Genome Research, Vol. 6, Issue 10, p. 986-994 https://doi.org/10.1101/gr.6.10.986	journal	October 1996
DNA Polymerase γ, The Mitochondrial Replicase Kaguni, Laurie S. Annual Review of Biochemistry, Vol. 73, Issue 1 https://doi.org/10.1146/annurev.biochem.72.121801.161455	journal	June 2004
BAX supports the mitochondrial network, promoting bioenergetics in nonapoptotic cells Boohaker, Rebecca J.; Zhang, Ge; Carlson, Adina Loosley American Journal of Physiology-Cell Physiology, Vol. 300, Issue 6 https://doi.org/10.1152/ajpcell.00325.2010	journal	June 2011
Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy Kang, M. H.; Reynolds, C. P. Clinical Cancer Research, Vol. 15, Issue 4 https://doi.org/10.1158/1078-0432.ccr-08-0144	journal	February 2009
Defects in mitochondrial metabolism and cancer Gaude, Edoardo; Frezza, Christian Cancer & Metabolism, Vol. 2, Issue 1 https://doi.org/10.1186/2049-3002-2-10	journal	July 2014
p53 regulates mtDNA copy number and mitocheckpoint pathway Singh, KeshavK; Kulawiec, Mariola; Ayyasamy, Vanniarajan Journal of Carcinogenesis, Vol. 8, Issue 1 https://doi.org/10.4103/1477-3163.50893	journal	January 2009
ROS-mediated mechanisms of autophagy stimulation and their relevance in cancer therapy Dewaele, Michael; Maes, Hannelore; Agostinis, Patrizia Autophagy, Vol. 6, Issue 7 https://doi.org/10.4161/auto.6.7.12113	journal	October 2010
The selection of Chinese hamster cells deficient in oxidative energy metabolism Ditta, G.; Soderberg, K.; Landy, F. Somatic Cell Genetics, Vol. 2, Issue 4 https://doi.org/10.1007/BF01538838	journal	July 1976
Precision medicine in acute lymphoblastic leukemia Pui, Ching-Hon Frontiers of Medicine, Vol. 14, Issue 6 https://doi.org/10.1007/s11684-020-0759-8	journal	October 2020
Mitochondria and Cancer Prasun, Pankaj Mitochondrial Medicine https://doi.org/10.1016/b978-0-12-817006-9.00021-6	book	May 2019
ABT-199: Taking Dead Aim at BCL-2 Davids, Matthew S.; Letai, Anthony Cancer Cell, Vol. 23, Issue 2 https://doi.org/10.1016/j.ccr.2013.01.018	journal	February 2013
Mitochondria and Cancer Vyas, Sejal; Zaganjor, Elma; Haigis, Marcia C. Cell, Vol. 166, Issue 3 https://doi.org/10.1016/j.cell.2016.07.002	journal	July 2016
Mitochondria and Cancer St. Clair, Daret Free Radical Biology and Medicine, Vol. 87 https://doi.org/10.1016/j.freeradbiomed.2015.10.013	journal	October 2015
Oxidized Mitochondrial DNA Activates the NLRP3 Inflammasome during Apoptosis Shimada, Kenichi; Crother, Timothy R.; Karlin, Justin Immunity, Vol. 36, Issue 3 https://doi.org/10.1016/j.immuni.2012.01.009	journal	March 2012
Mitochondrial Cardiolipin Is Required for Nlrp3 Inflammasome Activation Iyer, Shankar S.; He, Qiong; Janczy, John R. Immunity, Vol. 39, Issue 2 https://doi.org/10.1016/j.immuni.2013.08.001	journal	August 2013
Transformations of the macromolecular landscape at mitochondria during DNA-damage-induced apoptotic cell death Yadav, N.; Pliss, A.; Kuzmin, A. Cell Death & Disease, Vol. 5, Issue 10 https://doi.org/10.1038/cddis.2014.405	journal	October 2014
ABT-199, a potent and selective BCL-2 inhibitor, achieves antitumor activity while sparing platelets Souers, Andrew J.; Leverson, Joel D.; Boghaert, Erwin R. Nature Medicine, Vol. 19, Issue 2 https://doi.org/10.1038/nm.3048	journal	January 2013
Mitochondrial functions during cell death, a complex (I–V) dilemma Ricci, J-E; Waterhouse, N.; Green, D. R. Cell Death & Differentiation, Vol. 10, Issue 5 https://doi.org/10.1038/sj.cdd.4401225	journal	May 2003
Novel role of p53 in maintaining mitochondrial genetic stability through interaction with DNA Pol γ Achanta, Geetha; Sasaki, Ryohei; Feng, Li The EMBO Journal, Vol. 24, Issue 19 https://doi.org/10.1038/sj.emboj.7600819	journal	September 2005
Bcl-2 and Mitochondrial Oxygen Radicals: NEW APPROACHES WITH REACTIVE OXYGEN SPECIES-SENSITIVE PROBES Esposti, Mauro Degli; Hatzinisiriou, Irene; McLennan, Holly Journal of Biological Chemistry, Vol. 274, Issue 42 https://doi.org/10.1074/jbc.274.42.29831	journal	October 1999
Lack of Oxidative Phosphorylation and Low Mitochondrial Membrane Potential Decrease Susceptibility to Apoptosis and Do Not Modulate the Protective Effect of Bcl-x _L in Osteosarcoma Cells Dey, Runu; Moraes, Carlos T. Journal of Biological Chemistry, Vol. 275, Issue 10 https://doi.org/10.1074/jbc.275.10.7087	journal	March 2000
Mitochondrial Dysfunction Impairs Tumor Suppressor p53 Expression/Function Compton, Shannon; Kim, Chul; Griner, Nicholas B. Journal of Biological Chemistry, Vol. 286, Issue 23 https://doi.org/10.1074/jbc.M110.163063	journal	April 2011
Early Mitochondrial Activation and Cytochrome c Up-regulation during Apoptosis Chandra, Dhyan; Liu, Jun-Wei; Tang, Dean G. Journal of Biological Chemistry, Vol. 277, Issue 52 https://doi.org/10.1074/jbc.M207622200	journal	October 2002
Mitochondrially Localized Active Caspase-9 and Caspase-3 Result Mostly from Translocation from the Cytosol and Partly from Caspase-mediated Activation in the Organelle: LACK OF EVIDENCE FOR Apaf-1-MEDIATED PROCASPASE-9 ACTIVATION IN THE MITOCHONDRIA Chandra, Dhyan; Tang, Dean G. Journal of Biological Chemistry, Vol. 278, Issue 19 https://doi.org/10.1074/jbc.M300750200	journal	February 2003
Lipopolysaccharide Stimulates Mitochondrial Biogenesis via Activation of Nuclear Respiratory Factor-1 Suliman, Hagir B.; Carraway, Martha S.; Welty-Wolf, Karen E. Journal of Biological Chemistry, Vol. 278, Issue 42 https://doi.org/10.1074/jbc.M304719200	journal	August 2003
The Mitochondrial Production of Reactive Oxygen Species: Mechanisms and Implications in Human Pathology Lenaz, Giorgio IUBMB Life (International Union of Biochemistry and Molecular Biology: Life), Vol. 52, Issue 3-5 https://doi.org/10.1080/15216540152845957	journal	September 2001
Mitochondria as Therapeutic Targets for the Treatment of Malignant Disease Fulda, Simone; Kroemer, Guido Antioxidants & Redox Signaling, Vol. 15, Issue 12 https://doi.org/10.1089/ars.2011.4078	journal	December 2011
DNA supercoiling suppresses real-time PCR: a new approach to the quantification of mitochondrial DNA damage and repair Chen, Jinsong; Kadlubar, Fred F.; Chen, Junjian Z. Nucleic Acids Research, Vol. 35, Issue 4 https://doi.org/10.1093/nar/gkm010	journal	February 2007
The role of the ESSS protein in the assembly of a functional and stable mammalian mitochondrial complex I (NADH-ubiquinone oxidoreductase): Mammalian cells with severe complex I deficiency Potluri, Prasanth; Yadava, Nagendra; Scheffler, Immo E. European Journal of Biochemistry, Vol. 271, Issue 15 https://doi.org/10.1111/j.1432-1033.2004.04260.x	journal	July 2004
Bcl-2 Inhibitors: Targeting Mitochondrial Apoptotic Pathways in Cancer Therapy Kang, M. H.; Reynolds, C. P. Clinical Cancer Research, Vol. 15, Issue 4 https://doi.org/10.1158/1078-0432.CCR-08-0144	journal	February 2009
Decreased mitochondrial DNA content in blood samples of patients with stage I breast cancer Xia, Peng; An, Han-Xiang; Dang, Cheng-Xue BMC Cancer, Vol. 9, Issue 1 https://doi.org/10.1186/1471-2407-9-454	journal	December 2009
Mitochondria and cancer Chandel, Navdeep S. Cancer & Metabolism, Vol. 2, Issue 1 https://doi.org/10.1186/2049-3002-2-8	journal	June 2014
Staging the Tumor and Staging the Host: Pretreatment Combined Neutrophil Lymphocyte Ratio and Modified Glasgow Prognostic Score Is Associated with Overall Survival in Patients with Esophagogastric Cancers Undergoing Treatment with Curative Intent McSorley, Stephen T.; Lau, Hiu Y. N.; McIntosh, David Annals of Surgical Oncology, Vol. 28, Issue 2 https://doi.org/10.1245/s10434-020-09074-5	journal	September 2020
Etoposide Induces ATM-Dependent Mitochondrial Biogenesis through AMPK Activation Fu, Xuan; Wan, Shan; Lyu, Yi Lisa PLoS ONE, Vol. 3, Issue 4 https://doi.org/10.1371/journal.pone.0002009	journal	April 2008

Cited By (22)

The Lipid Side of Bone Marrow Adipocytes: How Tumor Cells Adapt and Survive in Bone Diedrich, Jonathan D.; Herroon, Mackenzie K.; Rajagurubandara, Erandi Current Osteoporosis Reports, Vol. 16, Issue 4 https://doi.org/10.1007/s11914-018-0453-9	journal	June 2018
Investigation of Mitochondrial Metabolic Response to Doxorubicin in Prostate Cancer Cells: An NADH, FAD and Tryptophan FLIM Assay Alam, Shagufta Rehman; Wallrabe, Horst; Svindrych, Zdenek Scientific Reports, Vol. 7, Issue 1 https://doi.org/10.1038/s41598-017-10856-3	journal	September 2017
Cytochrome c1 in ductal carcinomain situof breast associated with proliferation and comedo necrosis Chishiki, Mayuko; Takagi, Kiyoshi; Sato, Ai Cancer Science, Vol. 108, Issue 7 https://doi.org/10.1111/cas.13251	journal	May 2017
BA6 Induces Apoptosis via Stimulation of Reactive Oxygen Species and Inhibition of Oxidative Phosphorylation in Human Lung Cancer Cells Cheng, Meng-Hsuan; Huang, Hung-Ling; Lin, Yen-You Oxidative Medicine and Cellular Longevity, Vol. 2019 https://doi.org/10.1155/2019/6342104	journal	May 2019
Antioxidant Effects and Mechanisms of Medicinal Plants and Their Bioactive Compounds for the Prevention and Treatment of Type 2 Diabetes: An Updated Review Unuofin, Jeremiah Oshiomame; Lebelo, Sogolo Lucky Oxidative Medicine and Cellular Longevity, Vol. 2020 https://doi.org/10.1155/2020/1356893	journal	February 2020
Enhanced Proapoptotic Effects of Water Dispersed Complexes of 4-Thiazolidinone-Based Chemotherapeutics with a PEG-Containing Polymeric Nanocarrier Kobylinska, L.; Ivasechko, I.; Skorokhyd, N. Nanoscale Research Letters, Vol. 14, Issue 1 https://doi.org/10.1186/s11671-019-2945-7	journal	April 2019
Macrophage Migration Inhibitory Factor Secretion Is Induced by Ionizing Radiation and Oxidative Stress in Cancer Cells Gupta, Yashi; Pasupuleti, Vinay; Du, Weinan PLOS ONE, Vol. 11, Issue 1 https://doi.org/10.1371/journal.pone.0146482	journal	January 2016
Impact of Mediterranean diet on metabolic syndrome, cancer and longevity Di Daniele, Nicola; Noce, Annalisa; Vidiri, Maria Francesca Oncotarget, Vol. 8, Issue 5 https://doi.org/10.18632/oncotarget.13553	journal	November 2016
Correction: p53 and metabolism: from mechanism to therapeutics Simabuco, Fernando M.; Morale, Mirian G.; Pavan, Isadora C. B. Oncotarget, Vol. 9, Issue 74 https://doi.org/10.18632/oncotarget.26181	journal	September 2018
Inflammation and Metabolism in Cancer Cell—Mitochondria Key Player Neagu, Monica; Constantin, Carolina; Popescu, Iulia Dana Frontiers in Oncology, Vol. 9 https://doi.org/10.3389/fonc.2019.00348	journal	May 2019
BAP1 Status Determines the Sensitivity of Malignant Mesothelioma Cells to Gemcitabine Treatment Guazzelli, Alice; Meysami, Parisa; Bakker, Emyr International Journal of Molecular Sciences, Vol. 20, Issue 2 https://doi.org/10.3390/ijms20020429	journal	January 2019
Ginsenoside Rh2 and Rg3 inhibit cell proliferation and induce apoptosis by increasing mitochondrial reactive oxygen species in human leukemia Jurkat cells Xia, Ting; Wang, Ying-Nan; Zhou, Chuan-Xin Molecular Medicine Reports, Vol. 15, Issue 6 https://doi.org/10.3892/mmr.2017.6459	journal	April 2017
Metabolic underpinnings of leukemia pathology and treatment Nemkov, Travis; D'Alessandro, Angelo; Reisz, Julie A. CANCER REPORTS, Vol. 2, Issue 2 https://doi.org/10.1002/cnr2.1139	journal	October 2018
Reactive oxygen species (ROS) are a key determinant of cancer's metabolic phenotype: ROS are a key determinant of cancer's metabolic phenotype Rodic, Stefan; Vincent, Mark David International Journal of Cancer, Vol. 142, Issue 3 https://doi.org/10.1002/ijc.31069	journal	October 2017
Identification of novel prognostic alternative splicing signature in papillary renal cell carcinoma Duan, Yi; Zhang, Dong Journal of Cellular Biochemistry, Vol. 121, Issue 1 https://doi.org/10.1002/jcb.29314	journal	August 2019
Cytotoxic effect of Semialarium mexicanum (Miers) Mennega root bark extracts and fractions against breast cancer cells Maldonado-Cubas, Juan; San Martin-Martínez, Eduardo; Quiroz-Reyes, Cinthya Nathaly Physiology and Molecular Biology of Plants, Vol. 24, Issue 6 https://doi.org/10.1007/s12298-018-0580-x	journal	July 2018
Bile acid-induced “Minority MOMP” promotes esophageal carcinogenesis while maintaining apoptotic resistance via Mcl-1 Xu, Yuan; Surman, Deborah R.; Diggs, Laurence Oncogene, Vol. 39, Issue 4 https://doi.org/10.1038/s41388-019-1029-6	journal	September 2019
Oxidative Stress and Carcinogenesis: Potential of Phytochemicals in Breast Cancer Therapy Forcados, Gilead Ebiegberi; James, Dorcas Bolanle; Sallau, Abdullahi Balarabe Nutrition and Cancer, Vol. 69, Issue 3 https://doi.org/10.1080/01635581.2017.1267777	journal	January 2017
Carboxyamidotriazole Synergizes with Sorafenib to Combat Non–Small Cell Lung Cancer through Inhibition of NANOG and Aggravation of Apoptosis Chen, Chen; Ju, Rui; Shi, Jing Journal of Pharmacology and Experimental Therapeutics, Vol. 362, Issue 2 https://doi.org/10.1124/jpet.117.240986	journal	May 2017
Resistance to neoadjuvant chemotherapy in triple-negative breast cancer mediated by a reversible drug-tolerant state Echeverria, Gloria V.; Ge, Zhongqi; Seth, Sahil Science Translational Medicine, Vol. 11, Issue 488 https://doi.org/10.1126/scitranslmed.aav0936	journal	April 2019
Targeting Oxidatively Induced DNA Damage Response in Cancer: Opportunities for Novel Cancer Therapies Davalli, Pierpaola; Marverti, Gaetano; Lauriola, Angela Oxidative Medicine and Cellular Longevity, Vol. 2018 https://doi.org/10.1155/2018/2389523	journal	January 2018
Sorafenib-Induced Apoptosis in Hepatocellular Carcinoma Is Reversed by SIRT1 Garten, Antje; Grohmann, Theresa; Kluckova, Katarina International Journal of Molecular Sciences, Vol. 20, Issue 16 https://doi.org/10.3390/ijms20164048	journal	August 2019

Similar Records

Tumor cell death induced by the inhibition of mitochondrial electron transport: The effect of 3-hydroxybakuchiol

Journal Article · Tue Oct 15 00:00:00 EDT 2013 · Toxicology and Applied Pharmacology · OSTI ID:22285428

Apaf-1 deficient mouse fibroblasts are resistant to MNNG and MMS-induced apoptotic death without attenuation of Bcl-2 decline

Journal Article · Thu Sep 01 00:00:00 EDT 2005 · Toxicology and Applied Pharmacology · OSTI ID:20721898

Induction of apoptosis by esculetin in human leukemia U937 cells through activation of JNK and ERK

Journal Article · Fri Feb 29 23:00:00 EST 2008 · Toxicology and Applied Pharmacology · OSTI ID:21077936

Related Subjects

59 BASIC BIOLOGICAL SCIENCES

Oxidative phosphorylation-dependent regulation of cancer cell apoptosis in response to anticancer agents

Citation Formats

References (63)

Cited By (22)

Similar Records

Related Subjects