Hesperetin Induces the Apoptosis of Gastric Cancer Cells via Activating Mitochondrial Pathway by Increasing Reactive Oxygen Species

Digestive Diseases and Sciences

Volumn 60, Issue 10, 2015, Pages 2985-2995

  Zhang, Jixiang ^a   Wu, Dandan ^a   Vikash, ^a   Song, Jia ^a   Wang, Jing ^a   Yi, Jiasheng ^a   Dong, Weiguo ^a  

^a RENMIN HOSPITAL OF WUHAN UNIVERSITY   (China)

Author keywords

Apoptosis; Gastric cancer; Hesperetin; Mitochondria; Reactive oxygen species

Indexed keywords

4 [5 (4 METHYL 1 PIPERAZINYL)[2,5' BI 1H BENZIMIDAZOL] 2' YL]PHENOL; ACETYLCYSTEINE; APOPTOTIC PROTEASE ACTIVATING FACTOR 1; CASPASE 3; CASPASE 9; CYTOCHROME C; HESPERETIN; PROTEIN BAX; PROTEIN BCL 2; REACTIVE OXYGEN METABOLITE; HESPERIDIN;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ANTINEOPLASTIC ACTIVITY; APOPTOSIS; ARTICLE; CANCER CELL; CANCER INHIBITION; CELL COUNTING; CELL PROLIFERATION; CELL VIABILITY; CONTROLLED STUDY; DOSE RESPONSE; DRUG MECHANISM; HUMAN; HUMAN CELL; IN VIVO STUDY; MALE; MITOCHONDRIAL MEMBRANE POTENTIAL; MITOCHONDRION; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN EXPRESSION; STAINING; STOMACH CANCER; TUMOR XENOGRAFT; WESTERN BLOTTING; ANALYSIS OF VARIANCE; ANIMAL; BAGG ALBINO MOUSE; DRUG EFFECTS; FEMALE; METABOLISM; PATHOLOGY; PHYSIOLOGY; REFERENCE VALUE; STOMACH TUMOR; TUMOR CELL CULTURE; TUNEL ASSAY; XENOGRAFT;

ANALYSIS OF VARIANCE; ANIMALS; APOPTOSIS; BLOTTING, WESTERN; CELL PROLIFERATION; FEMALE; HESPERIDIN; HETEROGRAFTS; HUMANS; IN SITU NICK-END LABELING; MALE; MEMBRANE POTENTIAL, MITOCHONDRIAL; MICE; MICE, INBRED BALB C; REACTIVE OXYGEN SPECIES; REFERENCE VALUES; STOMACH NEOPLASMS; TUMOR CELLS, CULTURED;

EID: 84942198111     PISSN: 01632116     EISSN: 15732568     Source Type: Journal    
DOI: 10.1007/s10620-015-3696-7     Document Type: Article

References (46)

1. Siegel R, Ma J, Zou Z, Jemal A. Cancer statistics, 2014. CA Cancer J Clin. 2014;64:9–29.
2. Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer. 2015;136:E359–E386.
3. Herszényi L, Tulassay Z. Epidemiology of gastrointestinal and liver tumors. Eur Rev Med Pharmacol Sci. 2010;14:249–258.
4. Yu J, Gao J, Lu Z, Li Y, Shen L. Serum levels of TUBB3 correlate with clinical outcome in Chinese patients with advanced gastric cancer receiving first-line paclitaxel plus capecitabine. Med Oncol. 2012;29:3029–3034.
5. Seo JH, Jeong ES, Lee KS, Heo SH, Jeong DG, Choi YK. Lentivirus-mediated shRNA targeting of cyclin D1 enhances the chemosensitivity of human gastric cancer to 5-fluorouracil. Int J Oncol. 2013;43:2007–2014.
6. Xian XS, Park H, Choi MG, Park JM. Cannabinoid receptor agonist as an alternative drug in 5-fluorouracil-resistant gastric cancer cells. Anticancer Res. 2013;33:2541–2547.
7. Garg A, Garg S, Zaneveld LJ, Singla AK. Chemistry and pharmacology of the Citrus bioflavonoid hesperidin. Phytother Res. 2001;15:655–669.
8. Choi EJ. Hesperetin induced G1-phase cell cycle arrest in human breast cancer MCF-7 cells: involvement of CDK4 and p21. Nutr Cancer. 2007;59:115–119.
9. Cai Y, Luo Q, Sun M, Corke H. Antioxidant activity and phenolic compounds of 112 traditional Chinese medicinal plants associated with anticancer. Life Sci. 2004;74:2157–2184.
10. Sambantham S, Radha M, Paramasivam A, et al. Molecular mechanism underlying hesperetin-induced apoptosis by in silico analysis and in prostate cancer PC-3 cells. Asian Pac J Cancer Prev. 2013;14:4347–4352.
11. Ye L, Chan FL, Chen S, Leung LK. The citrus flavanone hesperetin inhibits growth of aromatase-expressing MCF-7 tumor in ovariectomized athymic mice. J Nutr Biochem. 2012;23:1230–1237.
12. Alshatwi AA, Ramesh E, Periasamy VS, Subash-Babu P. The apoptotic effect of hesperetin on human cervical cancer cells is mediated through cell cycle arrest, death receptor, and mitochondrial pathways. Fundam Clin Pharmacol. 2013;27:581–592.
13. Aranganathan S, Nalini N. Antiproliferative efficacy of hesperetin (citrus flavonoid) in 1,2-dimethylhydrazine-induced colon cancer. Phytother Res. 2013;27:999–1005.
14. Yang Y, Wolfram J, Shen H, Fang X, Ferrari M. Hesperetin: an inhibitor of the transforming growth factor-β (TGF-β) signaling pathway. Eur J Med Chem. 2012;58:390–395.
15. Yang Y, Wolfram J, Boom K, Fang X, Shen H, Ferrari M. Hesperetin impairs glucose uptake and inhibits proliferation of breast cancer cells. Cell Biochem Funct. 2013;31:374–379.
16. Patel PN, Yu XM, Jaskula-Sztul R, Chen H. Hesperetin activates the Notch1 signaling cascade, causes apoptosis, and induces cellular differentiation in anaplastic thyroid cancer. Ann Surg Oncol. 2014;21:S497–S504.
17. Zarebczan B, Pinchot SN, Kunnimalaiyaan M, Chen H. Hesperetin, a potential therapy for carcinoid cancer. Am J Surg. 2011;201:329–332; discussion 333.
18. Haidari F, Ali Keshavarz S, Reza Rashidi M, Mohammad Shahi M. Orange juice and hesperetin supplementation to hyperuricemic rats alter oxidative stress markers and xanthine oxidoreductase activity. J Clin Biochem Nutr. 2009;45:285–291.
19. Yang HL, Chen SC, Senthil Kumar KJ, et al. Antioxidant and anti-inflammatory potential of hesperetin metabolites obtained from hesperetin-administered rat serum: an ex vivo approach. J Agric Food Chem. 2012;60:522–532.
20. Zhang H, Gomez AM, Wang X, Yan Y, Zheng M, Cheng H. ROS regulation of microdomain Ca(2+) signalling at the dyads. Cardiovasc Res. 2013;98:248–258.
21. Sena LA, Chandel NS. Physiological roles of mitochondrial reactive oxygen species. Mol Cell. 2012;48:158–167.
22. Finkel T. Signal transduction by reactive oxygen species. J Cell Biol. 2011;194:7–15.
23. Grivennikova VG, Vinogradov AD. Mitochondrial production of reactive oxygen species. Biochemistry (Mosc). 2013;78:1490–1511.
24. Starkov AA. The role of mitochondria in reactive oxygen species metabolism and signaling. Ann NY Acad Sci. 2008;1147:37–52.
25. Chang MC, Chang HH, Chan CP, et al. p-Cresol affects reactive oxygen species generation, cell cycle arrest, cytotoxicity and inflammation/atherosclerosis-related modulators production in endothelial cells and mononuclear cells. PLoS One. 2014;9:e114446.
26. Rehman AU, Dugic E, Benham C, Lione L, Mackenzie LS. Selective inhibition of NADPH oxidase reverses the over contraction of diabetic rat aorta. Redox Biol. 2013;2C:61–64.
27. Prasad K, Dhar I. Oxidative stress as a mechanism of added sugar-induced cardiovascular disease. Int J Angiol. 2014;23:217–226.
28. Dhillon H, Chikara S, Reindl KM. Piperlongumine induces pancreatic cancer cell death by enhancing reactive oxygen species and DNA damage. Toxicol Rep. 2014;1:309–318.
29. Udensi UK, Tchounwou PB. Dual effect of oxidative stress on leukemia cancer induction and treatment. J Exp Clin Cancer Res. 2014;33:106.
30. Wang P, Xie K, Wang C, Bi J. Oxidative stress induced by lipid peroxidation is related with inflammation of demyelination and neurodegeneration in multiple sclerosis. Eur Neurol. 2014;72:249–254.
31. Nijland PG, Witte ME, van Het Hof B, et al. Astroglial PGC-1alpha increases mitochondrial antioxidant capacity and suppresses inflammation: implications for multiple sclerosis. Acta Neuropathol Commun. 2014;2:170.
32. Sivagami G, Vinothkumar R, Bernini R, et al. Role of hesperetin (a natural flavonoid) and its analogue on apoptosis in HT-29 human colon adenocarcinoma cell line—a comparative study. Food Chem Toxicol. 2012;50:660–671.
33. Choi EJ, Ahn WS. Neuroprotective effects of chronic hesperetin administration in mice. Arch Pharm Res. 2008;31:1457–1462.
34. Aranganathan S, Selvam JP, Nalini N. Effect of hesperetin, a citrus flavonoid, on bacterial enzymes and carcinogen-induced aberrant crypt foci in colon cancer rats: a dose-dependent study. J Pharm Pharmacol. 2008;60:1385–1392.
35. Perry SW, Norman JP, Barbieri J, Brown EB, Gelbard HA. Mitochondrial membrane potential probes and the proton gradient: a practical usage guide. Biotechniques. 2011;50:98–115.
36. Ly JD, Grubb DR, Lawen A. The mitochondrial membrane potential (deltapsi(m)) in apoptosis; an update. Apoptosis. 2003;8:115–128.
37. Solaini G, Sgarbi G, Lenaz G, Baracca A. Evaluating mitochondrial membrane potential in cells. Biosci Rep. 2007;27:11–21.
38. Green DR, Kroemer G. The pathophysiology of mitochondrial cell death. Science. 2004;305:626–629.
39. Chen Q, Lesnefsky EJ. Blockade of electron transport during ischemia preserves bcl-2 and inhibits opening of the mitochondrial permeability transition pore. FEBS Lett. 2011;585:921–926.
40. Halestrap AP, Doran E, Gillespie JP, O’Toole A. Mitochondria and cell death. Biochem Soc Trans. 2000;28:170–177.
41. Kim JY, Jung KJ, Choi JS, Chung HY. Hesperetin: a potent antioxidant against peroxynitrite. Free Radic Res. 2004;38:761–769.
42. Chen ZT, Chu HL, Chyau CC, Chu CC, Duh PD. Protective effects of sweet orange (Citrus sinensis) peel and their bioactive compounds on oxidative stress. Food Chem. 2012;135:2119–2127.
43. Jung HA, Jung MJ, Kim JY, Chung HY, Choi JS. Inhibitory activity of flavonoids from Prunus davidiana and other flavonoids on total ROS and hydroxyl radical generation. Arch Pharm Res. 2003;26:809–815.
44. Parhiz H, Roohbakhsh A, Soltani F, Rezaee R, Iranshahi M. Antioxidant and anti-inflammatory properties of the citrus flavonoids hesperidin and hesperetin: an updated review of their molecular mechanisms and experimental models. Phytother Res. 2015;29:323–331.
45. Palit S, Kar S, Sharma G, Das PK. Hesperetin induces apoptosis in breast carcinoma by triggering accumulation of ROS and activation of ASK1/JNK pathway. J Cell Physiol. 2014. doi:10.1002/jcp.24818.
46. Liu L, Fu J, Li T, et al. NG, a novel PABA/NO-based oleanolic acid derivative, induces human hepatoma cell apoptosis via a ROS/MAPK-dependent mitochondrial pathway. Eur J Pharmacol. 2012;691:61–68.