Mitochondria-targeted antioxidant and glycolysis inhibition: Synergistic therapy in hepatocellular carcinoma

Anti-Cancer Drugs

Volumn 24, Issue 9, 2013, Pages 881-888

  Dilip, Archana ^a   Cheng, Gang ^b   Joseph, Joy ^b   Kunnimalaiyaan, Selvi ^a   Kalyanaraman, Balaraman ^b   Kunnimalaiyaan, Muthusamy ^a   Gamblin, Thomas Clark ^a  

^a MEDICAL COLLEGE OF WISCONSIN   (United States)

^b FREE RADICAL RESEARCH CENTER   (United States)

Author keywords

apoptosis; combination therapy; glycolysis inhibitor; hepatocellular carcinoma; mitochondrial target; warburg effect

Indexed keywords

3 (4,5 DIMETHYL 2 THIAZOLYL) 2,5 DIPHENYLTETRAZOLIUM BROMIDE; ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENT; ANTIOXIDANT; CASPASE 3; CASPASE 7; DEOXYGLUCOSE; MITO CARBOXY PROXYL; NITROXIDE; UNCLASSIFIED DRUG;

APOPTOSIS; ARTICLE; BIOLUMINESCENCE; CANCER INHIBITION; CELL DEATH; CELL VIABILITY; CONTROLLED STUDY; CYTOTOXICITY; ENZYME ACTIVITY; GLYCOLYSIS; HUMAN; HUMAN CELL; IN VITRO STUDY; LIVER CELL; LIVER CELL CARCINOMA; MITOCHONDRION; PRIORITY JOURNAL; TARGET CELL;

ADENOSINE TRIPHOSPHATE; ANTINEOPLASTIC AGENTS; ANTIOXIDANTS; APOPTOSIS; CARCINOMA, HEPATOCELLULAR; CELL SURVIVAL; CELLS, CULTURED; CYCLIC N-OXIDES; DEOXYGLUCOSE; DRUG SYNERGISM; ENZYME INHIBITORS; GLYCOLYSIS; HEP G2 CELLS; HUMANS; KINETICS; LIVER; LIVER NEOPLASMS; MITOCHONDRIA, LIVER; MOLECULAR TARGETED THERAPY; NEOPLASM PROTEINS; ORGANOPHOSPHORUS COMPOUNDS;

EID: 84883451405     PISSN: 09594973     EISSN: 14735741     Source Type: Journal    
DOI: 10.1097/CAD.0b013e32836442c6     Document Type: Article

References (27)

1. Parikh S, Hyman D. Hepatocellular cancer: a guide for the internist. Am J Med 2007; 120:194-202.
2. Cahill BA, Braccia D. Current treatment for hepatocellular carcinoma. Clin J Oncol Nurs 2004; 8:393-399.
3. Villanueva A, Llovet JM. Targeted therapies for hepatocellular carcinoma. Gastroenterology 2011; 140:1410-1426.
4. Warburg O. On the origin of cancer cells. Science 1956; 123:309-314.
5. Warburg O, Wind F, Negelein E. The metabolism of tumors in the body. J Gen Physiol 1927; 8:519-530.
6. De Groof AJC, Lindert MMT, van Dommelen MMT, Wu M, Willemse M, Smift AL, et al. Increased OXPHOS activity precedes rise in glycolytic rate in H-RasV12/E1A transformed fibroblasts that develop a Warburg phenotype. Mol Cancer 2009; 8:54-68.
7. El Mjiyad N, Caro-Maldonado A, Ramirez-Peinado S, Munoz-Pinedo C. Sugar-free approaches to cancer cell killing. Oncogene 2011; 30:253-264.
8. Wang Q, Liang B, Shirwany NA, Zou MH. 2-Deoxy-D-glucose treatment of endothelial cells induces autophagy by reactive oxygen species-mediated activation of the AMP-activated protein kinase. PLoS One 2011; 6:e17234.
9. Dwarakanath BS, Singh D, Banerji AK, Sarin R, Venkataramana NK, Jalali R, et al. Clinical studies for improving radiotherapy with 2-deoxy-D-glucose: present status and future prospects. J Cancer Res Ther 2009; 5 (Suppl 1):S21-S26.
10. Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene 2006; 25:4633-4646.
11. Pathania D, Millard M, Neamati N. Opportunities in discovery and delivery of anticancer drugs targeting mitochondria and cancer cell metabolism. Adv Drug Deliv Rev 2009; 61:1250-1275.
12. Carew JS, Huang P. Mitochondrial defects in cancer. Mol Cancer 2002; 1:9-21.
13. Chen V, Staub RE, Fong S, Tagliaferri M, Cohen I, Shtivelman E. Bezielle selectively targets mitochondria of cancer cells to inhibit glycolysis and OXPHOS. PLoS One 2012; 7:e30300.
14. Kurtoglu M, Lampidis TJ. From delocalized lipophilic cations to hypoxia: blocking tumor cell mitochondrial function leads to therapeutic gain with glycolytic inhibitors. Mol Nutr Food Res 2009; 53:68-75.
15. Rao VA, Klein SR, Bonar SJ, Zielonka J, Mizuno N, Dickey JS, et al. The antioxidant transcription factor Nrf2 negatively regulates autophagy and growth arrest induced by the anticancer redox agent mitoquinone. J Biol Chem 2010; 285:34447-34459.
16. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, et al. Mitochondrial metabolism and ROS generation are essential for Krasmediated tumorigenicity. Proc Natl Acad Sci USA 2010; 107:8788-8793.
17. Cheng G, Zielonka J, Dranka BP, McAllister D, Mackinnon AC Jr, Joseph J, et al. Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death. Cancer Res 2012; 72:2634-2644.
18. Gueven N, Luff J, Peng C, Hosokawa K, Bottle SE, Lavin MF. Dramatic extension of tumor latency and correction of neurobehavioral phenotype in Atm-mutant mice with a nitroxide antioxidant. Free Radic Biol Med 2006; 41:992-1000.
19. Gariboldi MB, Ravizza R, Petterino C, Castagnaro M, Finocchiaro G, Monti E. Study of in vitro and in vivo effects of the piperidine nitroxide Tempol-a potential new therapeutic agent for gliomas. Eur J Cancer 2003; 39:829-837.
20. Yamaguchi R, Janssen E, Perkins G, Ellisman M, Kitada S, Reed JC. Efficient elimination of cancer cells by deoxyglucose-ABT-263/737 combination therapy. PLoS One 2011; 6:e24102.
21. Cheong JH, Park ES, Liang J, Dennison JB,Tsavachidou D, Nguyen-Charles C, et al. Dual inhibition of tumor energy pathway by 2-deoxyglucose and metformin is effective against a broad spectrum of preclinical cancer models. Mol Cancer Ther 2011; 10:2350-2362.
22. Cheng G, Lopez M, Zielonka J, Hauser AD, Joseph J, McAllister D, et al. Mitochondria-targeted nitroxides exacerbate fluvastatin-mediated cytostatic and cytotoxic effects in breast cancer cells. Cancer Biol Ther 2011; 12:707-717.
23. Qin JZ, Xin H, Nickoloff BJ. 2-Deoxyglucose sensitizes melanoma cells to TRAIL-induced apoptosis which is reduced by mannose. Biochem Biophys Res Commun 2010; 401:293-299.
24. Zagorodna O, Martin SM, Rutkowski DT, Kuwana T, Spitz DR, Knudson CM. 2-Deoxyglucose-induced toxicity is regulated by Bcl-2 family members and is enhanced by antagonizing Bcl-2 in lymphoma cell lines. Oncogene 2012; 31:2738-2749.
25. Cotter TG. Apoptosis and cancer: the genesis of a research field. Nat Rev Cancer 2009; 9:501-507.
26. Saraste A, Pulkki K. Morphologic and biochemical hallmarks of apoptosis. Cardiovasc Res 2000; 45:528-537.
27. Shi Y. Mechanisms of caspase activation and inhibition during apoptosis. Mol Cell 2002; 9:459-470.