Naringin induces autophagy-mediated growth inhibition by downregulating the PI3K/Akt/mTOR cascade via activation of MAPK pathways in AGS cancer cells

International Journal of Oncology

Volumn 47, Issue 3, 2015, Pages 1061-1069

  Raha, Suchismita ^a   Yumnam, Silvia ^a   Hong, Gyeong Eun ^a   Lee, Ho Jeong ^a   Saralamma, Venu Venkatarame Gowda ^a   Park, Hyeon Soo ^a   Heo, Jeong Doo ^b   Lee, Sang Joon ^b   Kim, Eun Hee ^c   Kim, Jin A ^c   Kim, Gon Sup ^a  

^a Gyeongsang National University   (South Korea)

^b Korea Institute of Toxicology   (South Korea)

^c International University of Korea   (South Korea)

Author keywords

AGS cells; Autophagy; Gastric carcinoma; Growth inhibition; MAPKs; Naringin

Indexed keywords

ANTINEOPLASTIC AGENT; AURANTIIN; BECLIN 1; LIGHT CHAIN 3 BETA; MAMMALIAN TARGET OF RAPAMYCIN; MITOGEN ACTIVATED PROTEIN KINASE; PHOSPHATIDYLINOSITOL 3 KINASE; PROTEIN; PROTEIN BAX; PROTEIN BCL XL; PROTEIN KINASE B; PROTEIN P21; UNCLASSIFIED DRUG; FLAVANONE DERIVATIVE; TARGET OF RAPAMYCIN KINASE;

ANTIPROLIFERATIVE ACTIVITY; APOPTOSIS; ARTICLE; AUTOPHAGOSOME; AUTOPHAGY; CANCER INHIBITION; CELL DEATH; CELL PROLIFERATION; CELL VACUOLE; CONTROLLED STUDY; DNA FRAGMENTATION; DOSE RESPONSE; DOWN REGULATION; ENZYME ACTIVATION; GASTRIC CANCER CELL LINE; HUMAN; HUMAN CELL; PRIORITY JOURNAL; PROTEIN EXPRESSION; PROTEIN PHOSPHORYLATION; SIGNAL TRANSDUCTION; STOMACH CANCER; STOMACH CARCINOMA; UPREGULATION; WESTERN BLOTTING; DRUG EFFECTS; GENE EXPRESSION REGULATION; METABOLISM; STOMACH NEOPLASMS; TUMOR CELL LINE;

ANTINEOPLASTIC AGENTS; AUTOPHAGY; CELL LINE, TUMOR; CELL PROLIFERATION; FLAVANONES; GENE EXPRESSION REGULATION, NEOPLASTIC; HUMANS; MAP KINASE SIGNALING SYSTEM; PHOSPHATIDYLINOSITOL 3-KINASE; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; STOMACH NEOPLASMS; TOR SERINE-THREONINE KINASES;

EID: 84938097560     PISSN: 10196439     EISSN: 17912423     Source Type: Journal    
DOI: 10.3892/ijo.2015.3095     Document Type: Article

References (51)

1. McLean MH and El-Omar EM: Genetics of gastric cancer. Nat Rev Gastroenterol Hepatol 11: 664-674, 2014.
2. World Health Organization. GLOBOCAN 2012: Estimated cancer incidence, mortality and prevalence worldwide in 2012. Available online: http://globocan.iarc.fr.
3. Torre LA, Bray F, Siegel RL, Ferlay J, Lortet-Tieulent J and Jemal A: Global cancer statistics, 2012. CA Cancer J Clin 65: 87-108, 2015.
4. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, Parkin DM, Forman D and Bray F: Cancer incidence and mortality worldwide: Sources, methods and major patterns in GLOBOCAN 2012. Int J Cancer 136: E359-E386, 2015.
5. Nagini S: Carcinoma of the stomach: A review of epidemiology, pathogenesis, molecular genetics and chemoprevention. World J Gastrointest Oncol 4: 156-169, 2012.
6. Hanahan D and Weinberg RA: Hallmarks of cancer: The next generation. Cell 144: 646-674, 2011.
7. Shaw RJ and Cantley LC: Ras, PI(3)K and mTOR signalling controls tumour cell growth. Nature 441: 424-430, 2006.
8. Xie X, White EP and Mehnert JM: Coordinate autophagy and mTOR pathway inhibition enhances cell death in melanoma. PLoS One 8: e55096, 2013.
9. Meijer AJ and Codogno P: Regulation and role of autophagy in mammalian cells. Int J Biochem Cell Biol 36: 2445-2462, 2004.
10. Gozuacik D and Kimchi A: Autophagy as a cell death and tumor suppressor mechanism. Oncogene 23: 2891-2906, 2004.
11. De A, De A, Papasian C, Hentges S, Banerjee S, Haque I and Banerjee SK: Emblica officinalis extract induces autophagy and inhibits human ovarian cancer cell proliferation, angiogenesis, growth of mouse xenograft tumors. PLoS One 8: e72748, 2013.
12. Law BY, Chan WK, Xu SW, Wang JR, Bai LP, Liu L and Wong VK: Natural small-molecule enhancers of autophagy induce autophagic cell death in apoptosis-defective cells. Sci Rep 4: 5510, 2014.
13. Hao W, Zhang X, Zhao W and Chen X: Psoralidin induces autophagy through ROS generation which inhibits the proliferation of human lung cancer A549 cells. Peer J 2: e555, 2014.
14. Xie CM, Chan WY, Yu S, Zhao J and Cheng CH: Bufalin induces autophagy-mediated cell death in human colon cancer cells through reactive oxygen species generation and JNK activation. Free Radic Biol Med 51: 1365-1375, 2011.
15. Chen YJ, Chi CW, Su WC and Huang HL: Lapatinib induces autophagic cell death and inhibits growth of human hepatocellular carcinoma. Oncotarget 5: 4845-4854, 2014.
16. Seger R and Krebs EG: The MAPK signaling cascade. FASEB J 9: 726-735, 1995.
17. Kim A, Yim NH and Ma JY: Samsoeum, a traditional herbal medicine, elicits apoptotic and autophagic cell death by inhibiting akt/mTOR and activating the JNK pathway in cancer cells. BMC Complement Altern Med 13: 233,6882-13-233, 2013.
18. Lee JW, Kim KS, An HK, Kim CH, Moon HI and Lee YC: Dendropanoxide induces autophagy through ERK1/2 activation in MG-63 human osteosarcoma cells and autophagy inhibition enhances dendropanoxide-induced apoptosis. PLoS One 8: e83611, 2013.
19. Sridharan S, Jain K and Basu A: Regulation of autophagy by kinases. Cancers (Basel) 3: 2630-2654, 2011.
20. Capparelli C, Chiavarina B, Whitaker-Menezes D, Pestell TG, Pestell RG, Hulit J, Andò S, Howell A, Martinez-Outschoorn UE, Sotgia F, et al: CDK inhibitors (p16/p19/p21) induce senescence and autophagy in cancer-associated fibroblasts, ?fueling? tumor growth via paracrine interactions, without an increase in neoangiogenesis. Cell Cycle 11: 3599-3610, 2012.
21. Abbas T and Dutta A: p21 in cancer: Intricate networks and multiple activities. Nat Rev Cancer 9: 400-414, 2009.
22. Yin YC, Lin CC, Chen TT, Chen JY, Tsai HJ, Wang CY and Chen SY: Clozapine induces autophagic cell death in non-small cell lung cancer cells. Cell Physiol Biochem 35: 945-956, 2015.
23. Ekor M: The growing use of herbal medicines: Issues relating to adverse reactions and challenges in monitoring safety. Front Pharmacol 4: 177, 2014.
24. Park KI, Park HS, Nagappan A, Hong GE, Lee H, Kang SR, Kim JA, Zhang J, Kim EH, Lee WS, et al: Induction of the cell cycle arrest and apoptosis by flavonoids isolated from Korean Citrus aurantium L. in non-small-cell lung cancer cells. Food Chem 135: 2728-2735, 2012.
25. Delle Monache S, Sanità P, Trapasso E, Ursino MR, Dugo P, Russo M, Ferlazzo N, Calapai G, Angelucci A and Navarra M: Mechanisms underlying the anti-tumoral effects of Citrus Bergamia juice. PLoS One 8: e61484, 2013.
26. Camargo CA, Gomes-Marcondes MC, Wutzki NC and Aoyama H: Naringin inhibits tumor growth and reduces interleukin-6 and tumor necrosis factor α levels i n rats with Walker 256 carcinosarcoma. Anticancer Res 32: 129-133, 2012.
27. Kumar A, Prakash A and Dogra S: Naringin alleviates cognitive impairment, mitochondrial dysfunction and oxidative stress induced by D-galactose in mice. Food Chem Toxicol 48: 626-632, 2010.
28. Lee EJ, Kim DI, Kim WJ and Moon SK: Naringin inhibits matrix metalloproteinase-9 expression and AKT phosphorylation in tumor necrosis factor-alpha-induced vascular smooth muscle cells. Mol Nutr Food Res 53: 1582-1591, 2009.
29. Nie YC, Wu H, Li PB, Luo YL, Long K, Xie LM, Shen JG and Su WW: Anti-inflammatory effects of naringin in chronic pulmonary neutrophilic inflammation in cigarette smokeexposed rats. J Med Food 15: 894-900, 2012.
30. Kanno S, Tomizawa A, Hiura T, Osanai Y, Shouji A, Ujibe M, Ohtake T, Kimura K and Ishikawa M: Inhibitory effects of naringenin on tumor growth in human cancer cell lines and sarcoma S-180-implanted mice. Biol Pharm Bull 28: 527-530, 2005.
31. Zeng L, Zhen Y, Chen Y, Zou L, Zhang Y, Hu F, Feng J, Shen J and Wei B: Naringin inhibits growth and induces apoptosis by a mechanism dependent on reduced activation of NF-κB/COX-2-caspase-1 pathway in HeLa cervical cancer cells. Int J Oncol 45: 1929-1936, 2014.
32. Rogakou EP, Nieves-Neira W, Boon C, Pommier Y and Bonner WM: Initiation of DNA fragmentation during apoptosis induces phosphorylation of H2AX histone at serine 139. J Biol Chem 275: 9390-9395, 2000.
33. Mizushima N: Methods for monitoring autophagy. Int J Biochem Cell Biol 36: 2491-2502, 2004.
34. Li H, Yang B, Huang J, Xiang T, Yin X, Wan J, Luo F, Zhang L, Li H and Ren G: Naringin inhibits growth potential of human triple-negative breast cancer cells by targeting β-catenin signaling pathway. Toxicol Lett 220: 219-228, 2013.
35. Kim DI, Lee SJ, Lee SB, Park K, Kim WJ and Moon SK: Requirement for Ras/Raf/ERK pathway in naringin-induced G1-cell-cycle arrest via p21WAF1 expression. Carcinogenesis 29: 1701-1709, 2008.
36. Shi MD, Liao YC, Shih YW and Tsai LY: Nobiletin attenuates metastasis via both ERK and PI3K/Akt pathways in HGF-treated liver cancer HepG2 cells. Phytomedicine 20: 743-752, 2013.
37. Yumnam S, Park HS, Kim MK, Nagappan A, Hong GE, Lee HJ, Lee WS, Kim EH, Cho JH, Shin SC, et al: Hesperidin induces paraptosis like cell death in hepatoblatoma, HepG2 cells: Involvement of ERK1/2 MAPK. PLoS One 9: e101321, 2014.
38. Chahar MK, Sharma N, Dobhal MP and Joshi YC: Flavonoids: A versatile source of anticancer drugs. Pharmacogn Rev 5: 1-12, 2011.
39. Fuhr U and Kummert AL: The fate of naringin in humans: A key to grapefruit juice-drug interactions? Clin Pharmacol Ther 58: 365-373, 1995.
40. Kanno S, Shouji A, Asou K and Ishikawa M: Effects of naringin on hydrogen peroxide-induced cytotoxicity and apoptosis in P388 cells. J Pharmacol Sci 92: 166-170, 2003.
41. Ramesh E and Alshatwi AA: Naringin induces death receptor and mitochondria-mediated apoptosis in human cervical cancer (SiHa) cells. Food Chem Toxicol 51: 97-105, 2013.
42. Asnaghi L, Calastretti A, Bevilacqua A, D'Agnano I, Gatti G, Canti G, Delia D, Capaccioli S and Nicolin A: Bcl-2 phosphorylation and apoptosis activated by damaged microtubules require mTOR and are regulated by Akt. Oncogene 23: 5781-5791, 2004.
43. Park HS, Park KI, Lee DH, Kang SR, Nagappan A, Kim JA, Kim EH, Lee WS, Shin SC, Hah YS, et al: Polyphenolic extract isolated from Korean Lonicera japonica Thunb. induce G2/M cell cycle arrest and apoptosis in HepG2 cells: Involvements of PI3K/Akt and MAPKs. Food Chem Toxicol 50: 2407-2416, 2012.
44. Akl MR, Ayoub NM, Ebrahim HY, Mohyeldin MM, Orabi KY, Foudah AI and El Sayed KA: Araguspongine C induces autophagic death in breast cancer cells through suppression of c-Met and HER2 receptor tyrosine kinase signaling. Mar Drugs 13: 288-311, 2015.
45. Won SJ, Yen CH, Liu HS, Wu SY, Lan SH, Jiang-Shieh YF, Lin CN and Su CL: Justicidin A-induced autophagy flux enhances apoptosis of human colorectal cancer cells via class III PI3K and Atg5 pathway. J Cell Physiol 230: 930-946, 2015.
46. Lee WJ, Wu LF, Chen WK, Wang CJ and Tseng TH: Inhibitory effect of luteolin on hepatocyte growth factor/scatter factorinduced HepG2 cell invasion involving both MAPK/ERKs and PI3K-Akt pathways. Chem Biol Interact 160: 123-133, 2006.
47. Aryal P, Kim K, Park PH, Ham S, Cho J and Song K: Baicalein induces autophagic cell death through AMPK/ULK1 activation and downregulation of mTORC1 complex components in human cancer cells. FEBS J 281: 4644-4658, 2014.
48. Kang R, Zeh HJ, Lotze MT and Tang D: The Beclin 1 network regulates autophagy and apoptosis. Cell Death Differ 18: 571-580, 2011.
49. Li X, Li X, Wang J, Ye Z and Li JC: Oridonin up-regulates expression of P21 and induces autophagy and apoptosis in human prostate cancer cells. Int J Biol Sci 8: 901-912, 2012.
50. Cui Q, Tashiro S, Onodera S, Minami M and Ikejima T: Oridonin induced autophagy in human cervical carcinoma HeLa cells through Ras, JNK, and P38 regulation. J Pharmacol Sci 105: 317-325, 2007.
51. Mohapatra P, Preet R, Das D, Satapathy SR, Choudhuri T, Wyatt MD and Kundu CN: Quinacrine-mediated autophagy and apoptosis in colon cancer cells is through a p53- and p21-dependent mechanism. Oncol Res 20: 81-91, 2012.