Mitochondria-targeted vitamin E analogs inhibit breast cancer cell energy metabolism and promote cell death

BMC Cancer

Volumn 13, Issue , 2013, Pages

  Cheng, Gang ^a   Zielonka, Jacek ^a   McAllister, Donna M ^a   Mackinnon, A Craig ^b   Joseph, Joy ^a   Dwinell, Michael B ^b   Kalyanaraman, Balaraman ^a  

^a FREE RADICAL RESEARCH CENTER   (United States)

^b MEDICAL COLLEGE OF WISCONSIN   (United States)

Author keywords

Antiglycolytics; Bioenergetics; Breast cancer metabolism; Mitochondria; Mitochondria targeted drugs; Tocopherol; Triphenylphosphonium cations

Indexed keywords

ADENOSINE TRIPHOSPHATE; ALPHA TOCOPHEROL DERIVATIVE; DEOXYGLUCOSE; MITOCHROMANOL; MITOCHROMANOL ACETATE; UNCLASSIFIED DRUG; 2,2,5,7,8-PENTAMETHYL-1-HYDROXYCHROMAN; ALPHA TOCOPHEROL; CHROMAN DERIVATIVE;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; ARTICLE; BREAST CANCER; CANCER CELL; CANCER CELL CULTURE; CANCER INHIBITION; CELL DEATH; CELL LEVEL; COLONY FORMATION; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG ACCUMULATION; DRUG CYTOTOXICITY; DRUG POTENTIATION; DRUG SELECTIVITY; DRUG TARGETING; DRUG TISSUE LEVEL; ENERGY METABOLISM; FEMALE; GLYCOLYSIS; HUMAN; HUMAN CELL; IN VIVO STUDY; MITOCHONDRION; MOUSE; NONHUMAN; OXYGEN CONSUMPTION; TUMOR GROWTH; TUMOR XENOGRAFT; ANALOGS AND DERIVATIVES; ANIMAL; BREAST TUMOR; DRUG EFFECTS; DRUG SCREENING; HIGH PERFORMANCE LIQUID CHROMATOGRAPHY; METABOLISM; PATHOLOGY; TUMOR CELL LINE;

ANIMALS; BREAST NEOPLASMS; CELL DEATH; CELL LINE, TUMOR; CHROMANS; CHROMATOGRAPHY, HIGH PRESSURE LIQUID; ENERGY METABOLISM; FEMALE; HUMANS; MICE; MITOCHONDRIA; VITAMIN E; XENOGRAFT MODEL ANTITUMOR ASSAYS;

EID: 84878817212     PISSN: None     EISSN: 14712407     Source Type: Journal    
DOI: 10.1186/1471-2407-13-285     Document Type: Article

References (49)

1. Hsu PP, Sabatini DM. Cancer cell metabolism: Warburg and beyond. Cell 2008, 134:703-707. 10.1016/j.cell.2008.08.021, 18775299.
2. Barger JF, Plas DR. Balancing biosynthesis and bioenergetics: metabolic programs in oncogenesis. Endocr Relat Cancer 2010, 17:R287-R304. 10.1677/ERC-10-0106, 20699334.
3. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 2009, 324:1029-1033. 10.1126/science.1160809, 2849637, 19460998.
4. Cheng G, Zielonka J, Dranka BP, McAllister D, Mackinnon AC, Joseph J, Kalyanaraman B. Mitochondria-targeted drugs synergize with 2-deoxyglucose to trigger breast cancer cell death. Cancer Res 2012, 72:2634-2644. 10.1158/0008-5472.CAN-11-3928, 22431711.
5. Beckham TH, Lu P, Jones EE, Marrison T, Lewis CS, Cheng JC, Ramshesh VK, Beeson G, Beeson CC, Drake RR, Bielawska A, Bielawski J, Szulc ZM, Ogretmen B, Norris JS, Liu X. LCL124, a cationic analog of ceramide, selectively induces pancreatic cancer cell death by accumulating in mitochondria. J Pharmacol Exp Ther 2013, 344:167-178. 10.1124/jpet.112.199216, 23086228.
6. Wheeler HE, Maitland ML, Dolan ME, Cox NJ, Ratain MJ. Cancer pharmacogenomics: strategies and challenges. Nat Rev Genet 2013, 14:23-34.
7. Smith RA, Hartley RC, Murphy MP. Mitochondria-targeted small molecule therapeutics and probes. Antioxid Redox Signal 2011, 15:3021-3038. 10.1089/ars.2011.3969, 21395490.
8. Millard M, Pathania D, Shabaik Y, Taheri L, Deng J, Neamati N. Preclinical evaluation of novel triphenylphosphonium salts with broad-spectrum activity. PLoS One 2010, 5:e13131. 10.1371/journal.pone.0013131, 2949386, 20957228.
9. Ju J, Picinich SC, Yang Z, Zhao Y, Suh N, Kong AN, Yang CS. Cancer-preventive activities of tocopherols and tocotrienols. Carcinogenesis 2010, 31:533-542. 10.1093/carcin/bgp205, 2860705, 19748925.
10. Kunnumakkara AB, Sung B, Ravindran J, Diagaradjane P, Deorukhkar A, Dey S, Koca C, Yadav VR, Tong Z, Gelovani JG, Guha S, Krishnan S, Krishnan BB. {Gamma}-tocotrienol inhibits pancreatic tumors and sensitizes them to gemcitabine treatment by modulating the inflammatory microenvironment. Cancer Res 2010, 70:8695-8705. 10.1158/0008-5472.CAN-10-2318, 2970705, 20864511.
11. Li GX, Lee MJ, Liu AB, Yang Z, Lin Y, Shih WJ, Yang CS. delta-tocopherol is more active than alpha - or gamma -tocopherol in inhibiting lung tumorigenesis in vivo. Cancer Prev Res (Phila) 2011, 4:404-413.
12. Shah SJ, Sylvester PW. Gamma-tocotrienol inhibits neoplastic mammary epithelial cell proliferation by decreasing Akt and nuclear factor kappaB activity. Exp Biol Med (Maywood) 2005, 230:235-241.
13. Azzi A, Ricciarelli R, Zingg JM. Non-antioxidant molecular functions of alpha-tocopherol (vitamin E). FEBS Lett 2002, 519:8-10. 10.1016/S0014-5793(02)02706-0, 12023009.
14. Neuzil J, Tomasetti M, Zhao Y, Dong LF, Birringer M, Wang XF, Low P, Wu K, Salvatore BA, Ralph SJ. Vitamin E analogs, a novel group of " mitocans," as anticancer agents: the importance of being redox-silent. Mol Pharmacol 2007, 71:1185-1199. 10.1124/mol.106.030122, 17220355.
15. Dong LF, Freeman R, Liu J, Zobalova R, Marin-Hernandez A, Stantic M, Rohlena J, Valis K, Rodriguez-Enriquez S, Butcher B, Goodwin J, Brunk UT, Witting PK, Moreno-Sanchez R, Scheffler IE, Ralph SJ, Neuzil J. Suppression of tumor growth in vivo by the mitocan alpha-tocopheryl succinate requires respiratory complex II. Clin Cancer Res 2009, 15:1593-1600. 10.1158/1078-0432.CCR-08-2439, 19223492.
16. Dong LF, Jameson VJ, Tilly D, Cerny J, Mahdavian E, Marin-Hernandez A, Hernandez-Esquivel L, Rodriguez-Enriquez S, Stursa J, Witting PK, Stantic B, Rohlena J, Truksa J, Kluckova K, Dyason JC, Ledvina M, Salvatore BA, Moreno-Sánchez R, Coster MJ, Ralph SJ, Smith RA, Neuzil J. Mitochondrial targeting of vitamin E succinate enhances its pro-apoptotic and anti-cancer activity via mitochondrial complex II. J Biol Chem 2011, 286:3717-3728. 10.1074/jbc.M110.186643, 3030374, 21059645.
17. Wang F, Ogasawara MA, Huang P. Small mitochondria-targeting molecules as anti-cancer agents. Mol Aspects Med 2010, 31:75-92. 10.1016/j.mam.2009.12.003, 2836415, 19995573.
18. Dhanasekaran A, Kotamraju S, Kalivendi SV, Matsunaga T, Shang T, Keszler A, Joseph J, Kalyanaraman B. Supplementation of endothelial cells with mitochondria-targeted antioxidants inhibit peroxide-induced mitochondrial iron uptake, oxidative damage, and apoptosis. J Biol Chem 2004, 279:37575-37587. 10.1074/jbc.M404003200, 15220329.
19. Holliday DL, Speirs V. Choosing the right cell line for breast cancer research. Breast Cancer Res 2011, 13:215. 10.1186/bcr2889, 3236329, 21884641.
20. Kang Y, Siegel PM, Shu W, Drobnjak M, Kakonen SM, Cordon-Cardo C, Guise TA, Massague J. A multigenic program mediating breast cancer metastasis to bone. Cancer Cell 2003, 3:537-549. 10.1016/S1535-6108(03)00132-6, 12842083.
21. Minn AJ, Gupta GP, Siegel PM, Bos PD, Shu W, Giri DD, Viale A, Olshen AB, Gerald WL, Massague J. Genes that mediate breast cancer metastasis to lung. Nature 2005, 436:518-524. 10.1038/nature03799, 1283098, 16049480.
22. Wendt MK, Cooper AN, Dwinell MB. Epigenetic silencing of CXCL12 increases the metastatic potential of mammary carcinoma cells. Oncogene 2008, 27:1461-1471. 10.1038/sj.onc.1210751, 17724466.
23. Fischer EG, Stingl A, Kirkpatrick CJ. Migration assay for endothelial cells in multiwells. Application to studies on the effect of opioids. J Immunol Methods 1990, 128:235-239. 10.1016/0022-1759(90)90215-H, 2139083.
24. Franken NA, Rodermond HM, Stap J, Haveman J, van Bree C. Clonogenic assay of cells in vitro. Nat Protoc 2006, 1:2315-2319. 10.1038/nprot.2006.339, 17406473.
25. Dranka BP, Hill BG, Rley-Usmar VM. Mitochondrial reserve capacity in endothelial cells: the impact of nitric oxide and reactive oxygen species. Free Radic Biol Med 2010, 48:905-914. 10.1016/j.freeradbiomed.2010.01.015, 2860730, 20093177.
26. Nicholls DG, Rley-Usmar VM, Wu M, Jensen PB, Rogers GW, Ferrick DA. Bioenergetic profile experiment using C2C12 myoblast cells. J Vis Exp 2010, 46:e2511.
27. Nadakavukaren KK, Nadakavukaren JJ, Chen LB. Increased rhodamine 123 uptake by carcinoma cells. Cancer Res 1985, 45:6093-6099.
28. 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. 10.1002/mnfr.200700457, 2928140, 19072739.
29. Summerhayes IC, Lampidis TJ, Bernal SD, Nadakavukaren JJ, Nadakavukaren KK, Shepherd EL, Chen LB. Unusual retention of rhodamine 123 by mitochondria in muscle and carcinoma cells. Proc Natl Acad Sci USA 1982, 79:5292-5296. 10.1073/pnas.79.17.5292, 346882, 6752944.
30. Snow BJ, Rolfe FL, Lockhart MM, Frampton CM, O'Sullivan JD, Fung V, Smith RA, Murphy MP, Taylor KM. A double-blind, placebo-controlled study to assess the mitochondria-targeted antioxidant MitoQ as a disease-modifying therapy in Parkinson's disease. Mov Disord 2010, 25:1670-1674. 10.1002/mds.23148, 20568096.
31. Pelicano H, Martin DS, Xu RH, Huang P. Glycolysis inhibition for anticancer treatment. Oncogene 2006, 25:4633-4646. 10.1038/sj.onc.1209597, 16892078.
32. Elstrom RL, Bauer DE, Buzzai M, Karnauskas R, Harris MH, Plas DR, Zhuang H, Cinalli RM, Alavi A, Rudin CM, Thompson CB. Akt stimulates aerobic glycolysis in cancer cells. Cancer Res 2004, 64:3892-3899. 10.1158/0008-5472.CAN-03-2904, 15172999.
33. Dang CV. Links between metabolism and cancer. Genes Dev 2012, 26:877-890. 10.1101/gad.189365.112, 3347786, 22549953.
34. Marin-Hernandez A, Gallardo-Perez JC, Rodriguez-Enriquez S, Encalada R, Moreno-Sanchez R, Saavedra E. Modeling cancer glycolysis. Biochim Biophys Acta 1807, 2011:755-767.
35. Fan Y, Dickman KG, Zong WX. Akt and c-Myc differentially activate cellular metabolic programs and prime cells to bioenergetic inhibition. J Biol Chem 2010, 285:7324-7333. 10.1074/jbc.M109.035584, 2844180, 20018866.
36. Cairns RA, Harris IS, Mak TW. Regulation of cancer cell metabolism. Nat Rev Cancer 2011, 11:85-95.
37. 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. 10.1016/j.addr.2009.05.010, 19716393.
38. Weinberg F, Hamanaka R, Wheaton WW, Weinberg S, Joseph J, Lopez M, Kalyanaraman B, Mutlu GM, Budinger GR, Chandel NS. Mitochondrial metabolism and ROS generation are essential for Kras-mediated tumorigenicity. Proc Natl Acad Sci USA 2010, 107:8788-8793. 10.1073/pnas.1003428107, 2889315, 20421486.
39. Wei S, Kulp SK, Chen CS. Energy restriction as an antitumor target of thiazolidinediones. J Biol Chem 2010, 285:9780-9791. 10.1074/jbc.M109.065466, 2843227, 20093366.
40. Sauna ZE, Smith MM, Muller M, Kerr KM, Ambudkar SV. The mechanism of action of multidrug-resistance-linked P-glycoprotein. J Bioenerg Biomembr 2001, 33:481-491. 10.1023/A:1012875105006, 11804190.
41. Zhou Y, Tozzi F, Chen J, Fan F, Xia L, Wang J, Gao G, Zhang A, Xia X, Brasher H, Widger W, Ellis LM, Weihua Z. Intracellular ATP levels are a pivotal determinant of chemoresistance in colon cancer cells. Cancer Res 2012, 72:304-314. 10.1158/0008-5472.CAN-11-1674, 3601736, 22084398.
42. Prochazka L, Koudelka S, Dong LF, Stursa J, Goodwin J, Neca J, Slavik J, Ciganek M, Masek J, Kluckova K, Nguyen M, Turanek J, Neuzil J. Mitochondrial targeting overcomes ABCA1-dependent resistance of lung carcinoma to alpha-tocopheryl succinate. Apoptosis 2013, 18:286-299. 10.1007/s10495-012-0795-1, 23299931.
43. Lopes MA, Meisel A, Carvalho FD, Bastos ML. Neuronal nitric oxide synthase is a key factor in doxorubicin-induced toxicity to rat-isolated cortical neurons. Neurotox Res 2011, 19:14-22. 10.1007/s12640-009-9135-9, 19924493.
44. Gianni L, Salvatorelli E, Minotti G. Anthracycline cardiotoxicity in breast cancer patients: synergism with trastuzumab and taxanes. Cardiovasc Toxicol 2007, 7:67-71. 10.1007/s12012-007-0013-5, 17652806.
45. Mao G, Kraus GA, Kim I, Spurlock ME, Bailey TB, Beitz DC. Effect of a mitochondria-targeted vitamin E derivative on mitochondrial alteration and systemic oxidative stress in mice. Br J Nutr 2011, 106:87-95. 10.1017/S0007114510005830, 21324214.
46. Chandran K, Aggarwal D, Migrino RQ, Joseph J, McAllister D, Konorev EA, Antholine WE, Zielonka J, Srinivasan S, Avadhani NG, Kalyanaraman B. Doxorubicin inactivates myocardial cytochrome c oxidase in rats: cardioprotection by Mito-Q. Biophys J 2009, 96:1388-1398. 10.1016/j.bpj.2008.10.042, 2717244, 19217856.
47. Mukhopadhyay P, Horvath B, Zsengeller Z, Zielonka J, Tanchian G, Holovac E, Kechrid M, Patel V, Stillman IE, Parikh SM, Joseph J, Kalyanaraman B, Pacher P. Mitochondrial-targeted antioxidants represent a promising approach for prevention of cisplatin-induced nephropathy. Free Radic Biol Med 2012, 52:497-506. 10.1016/j.freeradbiomed.2011.11.001, 3253235, 22120494.
48. Gohil VM, Sheth SA, Nilsson R, Wojtovich AP, Lee JH, Perocchi F, Chen W, Clish CB, Ayata C, Brookes PS, Mootha VK. Nutrient-sensitized screening for drugs that shift energy metabolism from mitochondrial respiration to glycolysis. Nat Biotechnol 2010, 28:249-255. 3135002, 20160716.
49. Hernlund E, Ihrlund LS, Khan O, Ates YO, Linder S, Panaretakis T, Shoshan MC. Potentiation of chemotherapeutic drugs by energy metabolism inhibitors 2-deoxyglucose and etomoxir. Int J Cancer 2008, 123:476-483. 10.1002/ijc.23525, 18452174.