Genipin-induced inhibition of uncoupling protein-2 sensitizes drug-resistant cancer cells to cytotoxic agents

PLoS ONE

Volumn 5, Issue 10, 2010, Pages

  Mailloux, Ryan J ^a   Adjeitey, Cyril Nii Klu ^a   Harper, Mary Ellen ^a  

^a UNIVERSITY OF OTTAWA   (Canada)

Author keywords

[No Author keywords available]

Indexed keywords

DICHLORODIHYDROFLUORESCEIN DIACETATE; DOXORUBICIN; EPIRUBICIN; GENIPIN; MENADIONE; REACTIVE OXYGEN METABOLITE; UNCOUPLING PROTEIN 2; ANTHRACYCLINE; ANTINEOPLASTIC AGENT; ION CHANNEL; IRIDOID; MITOCHONDRIAL PROTEIN; MITOCHONDRIAL UNCOUPLING PROTEIN 2;

ARTICLE; CANCER CELL; CELL DEATH; CELL SPECIFICITY; CELL TYPE; CELL VIABILITY; CONCENTRATION RESPONSE; CONTROLLED STUDY; CYTOFLUOROMETRY; DRUG EFFECT; DRUG MECHANISM; DRUG POTENTIATION; DRUG RESISTANCE; DRUG SENSITIZATION; HUMAN; HUMAN CELL; MITOCHONDRIAL RESPIRATION; OXYGEN CONSUMPTION; PROTEIN EXPRESSION; PROTEIN LOCALIZATION; STABLE EXPRESSION; DRUG ANTAGONISM; FLUOROMETRY; METABOLISM; TUMOR CELL LINE;

ANTHRACYCLINES; ANTINEOPLASTIC AGENTS; CELL LINE, TUMOR; DRUG RESISTANCE, NEOPLASM; DRUG SYNERGISM; FLUOROMETRY; HUMANS; ION CHANNELS; IRIDOID GLYCOSIDES; MITOCHONDRIAL PROTEINS; REACTIVE OXYGEN SPECIES;

EID: 78149459962     PISSN: None     EISSN: 19326203     Source Type: Journal    
DOI: 10.1371/journal.pone.0013289     Document Type: Article

References (53)

1. Crazzolara R, Bendall L (2009) Emerging treatments in acute lymphoblastic leukemia. Curr Cancer Drug Targets 9: 19-31.
2. Pilkington GJ, Parker K, Murray SA (2008) Approaches to mitochondrially mediated cancer therapy. Semin Cancer Biol 18: 226-235.
3. Tortora G, Bianco R, Daniele G, Ciardiello F, McCubrey JA, et al. (2007) Overcoming resistance to molecularly targeted anticancer therapies: Rational drug combinations based on EGFR and MAPK inhibition for solid tumours and haematologic malignancies. Drug Resist Updat 10: 81-100.
4. Trachootham D, Alexandre J, Huang P (2009) Targeting cancer cells by ROSmediated mechanisms: a radical therapeutic approach? Nat Rev Drug Discov 8: 579-591.
5. Kitano H (2004) Cancer as a robust system: implications for anticancer therapy. Nat Rev Cancer 4: 227-235.
6. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB (2008) The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7: 11-20.
7. Muller I, Niethammer D, Bruchelt G (1998) Anthracycline-derived chemotherapeutics in apoptosis and free radical cytotoxicity (Review). Int J Mol Med 1: 491-494.
8. Suzuki YJ, Edmondson JD, Ford GD (1992) Inactivation of rabbit muscle creatine kinase by hydrogen peroxide. Free Radic Res Commun 16: 131-136.
9. Barnett YA, King CM (1995) An investigation of antioxidant status, DNA repair capacity and mutation as a function of age in humans. Mutat Res 338: 115-128.
10. Harper ME, Antoniou A, Villalobos-Menuey E, Russo A, Trauger R, et al. (2002) Characterization of a novel metabolic strategy used by drug-resistant tumor cells. Faseb J 16: 1550-1557.
11. Baffy G (2010) Uncoupling protein-2 and cancer. Mitochondrion 10: 243-252.
12. Pecqueur C, Alves-Guerra C, Ricquier D, Bouillaud F (2009) UCP2, a metabolic sensor coupling glucose oxidation to mitochondrial metabolism? IUBMB Life 61: 762-767.
13. Negre-Salvayre A, Hirtz C, Carrera G, Cazenave R, Troly M, et al. (1997) A role for uncoupling protein-2 as a regulator of mitochondrial hydrogen peroxide generation. Faseb J 11: 809-815.
14. Parker N, Vidal-Puig A, Brand MD (2008) Stimulation of mitochondrial proton conductance by hydroxynonenal requires a high membrane potential. Biosci Rep 28: 83-88.
15. Diao J, Allister EM, Koshkin V, Lee SC, Bhattacharjee A, et al. (2008) UCP2 is highly expressed in pancreatic alpha-cells and influences secretion and survival. Proc Natl Acad Sci U S A 105: 12057-12062.
16. Carew JS, Huang P (2002) Mitochondrial defects in cancer. Mol Cancer 1: 9.
17. Sipos I, Tretter L, Adam-Vizi V (2003) The production of reactive oxygen species in intact isolated nerve terminals is independent of the mitochondrial membrane potential. Neurochem Res 28: 1575-1581.
18. Chance B, Sies H, Boveris A (1979) Hydroperoxide metabolism in mammalian organs. Physiol Rev 59: 527-605.
19. Korshunov SS, Skulachev VP, Starkov AA (1997) High protonic potential actuates a mechanism of production of reactive oxygen species in mitochondria. FEBS Lett 416: 15-18.
20. Barrientos A, Moraes CT (1999) Titrating the effects of mitochondrial complex I impairment in the cell physiology. J Biol Chem 274: 16188-16197.
21. Santandreu FM, Valle A, Fernandez de Mattos S, Roca P, Oliver J (2009) Hydrogen peroxide regulates the mitochondrial content of uncoupling protein 5 in colon cancer cells. Cell Physiol Biochem 24: 379-390.
22. Collins P, Bing C, McCulloch P, Williams G (2002) Muscle UCP-3 mRNA levels are elevated in weight loss associated with gastrointestinal adenocarcinoma in humans. Br J Cancer 86: 372-375.
23. Mattiasson G, Shamloo M, Gido G, Mathi K, Tomasevic G, et al. (2003) Uncoupling protein-2 prevents neuronal death and diminishes brain dysfunction after stroke and brain trauma. Nat Med 9: 1062-1068.
24. McLeod CJ, Aziz A, Hoyt RF, Jr., McCoy JP, Jr., Sack MN (2005) Uncoupling proteins 2 and 3 function in concert to augment tolerance to cardiac ischemia. J Biol Chem 280: 33470-33476.
25. Arsenijevic D, Onuma H, Pecqueur C, Raimbault S, Manning BS, et al. (2000) Disruption of the uncoupling protein-2 gene in mice reveals a role in immunity and reactive oxygen species production. Nat Genet 26: 435-439.
26. Krauss S, Zhang CY, Lowell BB (2002) A significant portion of mitochondrial proton leak in intact thymocytes depends on expression of UCP2. Proc Natl Acad Sci U S A 99: 118-122.
27. Echtay KS, Murphy MP, Smith RA, Talbot DA, Brand MD (2002) Superoxide activates mitochondrial uncoupling protein 2 from the matrix side. Studies using targeted antioxidants. J Biol Chem 277: 47129-47135.
28. Samudio I, Fiegl M, Andreeff M (2009) Mitochondrial uncoupling and the Warburg effect: molecular basis for the reprogramming of cancer cell metabolism. Cancer Res 69: 2163-2166.
29. Horimoto M, Resnick MB, Konkin TA, Routhier J, Wands JR, et al. (2004) Expression of uncoupling protein-2 in human colon cancer. Clin Cancer Res 10: 6203-6207.
30. Carretero MV, Torres L, Latasa U, Garcia-Trevijano ER, Prieto J, et al. (1998) Transformed but not normal hepatocytes express UCP2. FEBS Lett 439: 55-58.
31. Savagner F, Franc B, Guyetant S, Rodien P, Reynier P, et al. (2001) Defective mitochondrial ATP synthesis in oxyphilic thyroid tumors. J Clin Endocrinol Metab 86: 4920-4925.
32. Santandreu FM, Roca P, Oliver J (2010) Uncoupling protein-2 knockdown mediates the cytotoxic effects of cisplatin. Free Radic Biol Med 49: 658-666.
33. Derdak Z, Mark NM, Beldi G, Robson SC, Wands JR, et al. (2008) The mitochondrial uncoupling protein-2 promotes chemoresistance in cancer cells. Cancer Res 68: 2813-2819.
34. Parton LE, Ye CP, Coppari R, Enriori PJ, Choi B, et al. (2007) Glucose sensing by POMC neurons regulates glucose homeostasis and is impaired in obesity. Nature 449: 228-232.
35. Zhang CY, Parton LE, Ye CP, Krauss S, Shen R, et al. (2006) Genipin inhibits UCP2-mediated proton leak and acutely reverses obesity- and high glucoseinduced beta cell dysfunction in isolated pancreatic islets. Cell Metab 3: 417-427.
36. Collins P, Jones C, Choudhury S, Damelin L, Hodgson H (2005) Increased expression of uncoupling protein 2 in HepG2 cells attenuates oxidative damage and apoptosis. Liver Int 25: 880-887.
37. Thor H, Smith MT, Hartzell P, Bellomo G, Jewell SA, et al. (1982) The metabolism of menadione (2-methyl-1,4-naphthoquinone) by isolated hepatocytes. A study of the implications of oxidative stress in intact cells. J Biol Chem 257: 12419-12425.
38. Seifert EL, Bezaire V, Estey C, Harper ME (2008) Essential role for uncoupling protein-3 in mitochondrial adaptation to fasting but not in fatty acid oxidation or fatty acid anion export. J Biol Chem 283: 25124-25131.
39. Chang YC, Tseng TH, Lee MJ, Hsu JD, Wang CJ (2002) Induction of apoptosis by penta-acetyl geniposide in rat C6 glioma cells. Chem Biol Interact 141: 243-257.
40. Koo HJ, Lim KH, Jung HJ, Park EH (2006) Anti-inflammatory evaluation of gardenia extract, geniposide and genipin. J Ethnopharmacol 103: 496-500.
41. Kim BC, Kim HG, Lee SA, Lim S, Park EH, et al. (2005) Genipin-induced apoptosis in hepatoma cells is mediated by reactive oxygen species/c-Jun NH2- terminal kinase-dependent activation of mitochondrial pathway. Biochem Pharmacol 70: 1398-1407.
42. Tetef M, Margolin K, Ahn C, Akman S, Chow W, et al. (1995) Mitomycin C and menadione for the treatment of lung cancer: a phase II trial. Invest New Drugs 13: 157-162.
43. Harker WG, Slade DL, Dalton WS, Meltzer PS, Trent JM (1989) Multidrug resistance in mitoxantrone-selected HL-60 leukemia cells in the absence of Pglycoprotein overexpression. Cancer Res 49: 4542-4549.
44. Dang CV (2010) Rethinking the Warburg effect with Myc micromanaging glutamine metabolism. Cancer Res 70: 859-862.
45. Zhou H, Zhao J, Zhang X (2009) Inhibition of uncoupling protein 2 by genipin reduces insulin-stimulated glucose uptake in 3T3-L1 adipocytes. Arch Biochem Biophys 486: 88-93.
46. Echtay KS, Esteves TC, Pakay JL, Jekabsons MB, Lambert AJ, et al. (2003) A signalling role for 4-hydroxy-2-nonenal in regulation of mitochondrial uncoupling. Embo J 22: 4103-4110.
47. Swift LP, Rephaeli A, Nudelman A, Phillips DR, Cutts SM (2006) Doxorubicin- DNA adducts induce a non-topoisomerase II-mediated form of cell death. Cancer Res 66: 4863-4871.
48. Gouaze V, Mirault ME, Carpentier S, Salvayre R, Levade T, et al. (2001) Glutathione peroxidase-1 overexpression prevents ceramide production and partially inhibits apoptosis in doxorubicin-treated human breast carcinoma cells. Mol Pharmacol 60: 488-496.
49. Azzu V, Jastroch M, Divakaruni AS, Brand MD () The regulation and turnover of mitochondrial uncoupling proteins. Biochim Biophys Acta 74: 5463-5467.
50. Hurtaud C, Gelly C, Chen Z, Levi-Meyrueis C, Bouillaud F (2007) Glutamine stimulates translation of uncoupling protein 2mRNA. Cell Mol Life Sci 64: 1853-1860.
51. Wise DR, DeBerardinis RJ, Mancuso A, Sayed N, Zhang XY, et al. (2008) Myc regulates a transcriptional program that stimulates mitochondrial glutaminolysis and leads to glutamine addiction. Proc Natl Acad Sci U S A 105: 18782-18787.
52. Shannon JE (1978) Tissue culture viability assays-a review of the literature. Cryobiology 15: 239-241.
53. Mailloux RJ, Harper ME (2010) Glucose regulates enzymatic sources of mitochondrial NADPH in skeletal muscle cells; a novel role for glucose-6- phosphate dehydrogenase. Faseb J 24: 2495-2506.