(E)-2-Methoxy-4-(3-(4-Methoxyphenyl)Prop-1-en-1-yl)Phenol Induces Apoptosis in HeLa Cervical Cancer Cells via the Extrinsic Apoptotic Pathway
1
조회
0
다운로드
0
인용
0
참고문헌
키워드
초록
(E)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from butenal, is a recently synthesized Maillard reaction product. Owing to its novelty, little is known about the function of MMPP. In this study, we elucidated the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical cancer cell line, which is widely used in cancer research. We observed that MMPP was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9, without affecting the expression of the viral oncogenes E6 and E7. In particular, the expression of the death receptors DR5 and FAS was significantly increased by MMPP treatment. There were no significant alterations of mitochondrial intrinsic factors. Taking all these results together, our findings show that MMPP primarily induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic signaling pathway, accompanied by an enhanced expression of death receptors.
Abstract
(E)-2-Methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol (MMPP), derived from butenal, is a recently synthesized Maillard reaction product. Owing to its novelty, little is known about the function of MMPP. In this study, we elucidated the effects of MMPP on apoptosis in cervical cancer by using the HeLa cervical cancer cell line, which is widely used in cancer research. We observed that MMPP was cytotoxic to HeLa cells and induced activation of caspase-3, -8, and -9, without affecting the expression of the viral oncogenes E6 and E7. In particular, the expression of the death receptors DR5 and FAS was significantly increased by MMPP treatment. There were no significant alterations of mitochondrial intrinsic factors. Taking all these results together, our findings show that MMPP primarily induces apoptosis in HeLa cervical cancer cells via the extrinsic apoptotic signaling pathway, accompanied by an enhanced expression of death receptors.
참고문헌 (30)
- Ferlay J, "Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012", Int. J. Cancer, 136, pp.E359~E386 (2015)
- Wardak S., "Human papillomavirus (HPV) and cervical cancer", Med. Dosw. Mikrobiol, 68, pp.73~84 (2016)
- Eun-Kyoung Yim, "The Role of HPV E6 and E7 Oncoproteins in HPV-associated Cervical Carcinogenesis", Cancer Research and Treatment, 37(6), pp.319~324 (2005), 대한암학회
- Kwon T, "A1E reduces stemness and self-renewal in HPV 16-positive cervical cancer stem cells", BMC Complement. Altern. Med, 16, pp.42~ (2016)
- Elmore S., "Apoptosis: a review of programmed cell death", Toxicol. Pathol, 35, pp.495~516 (2007)
- Ouyang L, "Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis", Cell Prolif, 45, pp.487~498 (2012)
- Parrish AB, "Cellular mechanisms controlling caspase activation and function", Cold Spring Harb Perspect. Biol, 5, pp.a008672~ (2013)
- Son DJ, "Novel synthetic (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl) phenol inhibits arthritis by targeting signal transducer and activator of transcription 3", Sci. Rep, 6, pp.36852~ (2016)
- Jie Zheng, "(E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol suppresses ovarian cancer cell growth via inhibition of ERK and STAT3", Molecular Carcinogenesis, 56(9), pp.2003~2013 (2017), Wiley-Blackwell[DOI]
- Kim MS, "2,4-Bis (p-hydroxyphenyl)-2-butenal (HPB242) induces apoptosis via modulating E7 expression and inhibition of PI3K", Akt pathway in SiHa human cervical cancer cells, 2012, pp.64, 1236~1244
- 조승희, "(E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-jB", STAT3 pathway, 2014, pp.37(5), 652~661[DOI]
- Ung-Soo Lee, "Growth Inhibitory Effect of (E)-2,4-bis(p-hydroxyphenyl)-2-Butenal Diacetate through Induction of Apoptotic Cell Death by Increasing DR3 Expression in Human Lung Cancer Cells", Biomolecules & Therapeutics, 20(6), pp.538~543 (2012), 한국응용약물학회
- Kollipara PS, "(E)-2,4-bis(phydroxyphenyl)-2-butenal has an antiproliferative effect on NSCLC cells induced by p38 MAPK-mediated suppression of NF-kappaB and up-regulation of TNFRSF10B (DR5)", Br. J. Pharmacol, 168, pp.1471~1484 (2013)
- Masters JR, "HeLa cells 50 years on: the good, the bad and the ugly", Nat. Rev. Cancer, 2, pp.315~319 (2002)
- Dini L, "Multiple pathways for apoptotic nuclear fragmentation", Exp. Cell Res, 223, pp.340~347 (1996)
- Marino G, "Mechanisms of apoptotic phosphatidylserine exposure", Cell Res, 23, pp.1247~1248 (2013)
- Reutelingsperger CP, "Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and coagulation during apoptosis", Cell. Mol. Life Sci, 53, pp.527~532 (1997)
- Pucci B, "Cell cycle and apoptosis", Neoplasia, 2, pp.291~299 (2000)
- Chuang JY, "Induction of G0", G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells, 2005, pp.19, 683~688
- Hsiao CJ, "Cephalochromin induces G0", G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption, 2014, pp.77, 758~765
- Saralamma VV, "Poncirin induces apoptosis in AGS human gastric cancer cells through extrinsic apoptotic pathway by up-regulation of Fas ligand", Int. J. Mol. Sci, 16, pp.22676~22691 (2015)
- Kennedy RK, "5-Methyl phenazine-1-carboxylic acid:a novel bioactive metabolite by a rhizosphere soil bacterium that exhibits potent antimicrobial and anticancer activities", Chem. Biol. Interact, 231, pp.71~82 (2015)
- Wang K, "Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death", Sci. Rep, 6, pp.26064~ (2016)
- Fulda S, "Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy", Oncogene, 25, pp.4798~4811 (2006)
- Taylor RC, "Apoptosis: controlled demolition at the cellular level", Nat. Rev. Mol. Cell Biol, 9, pp.231~241 (2008)
- Porter AG, "Emerging roles of caspase-3 in apoptosis", Cell Death Differ, 6, pp.99~104 (1999)
- Walczak H., "Death receptor-ligand systems in cancer, cell death, and inflammation", Cold Spring Harb. Perspect. Biol, 5, pp.a008698~ (2013)
- Gao SY, "Dibromoacetic acid induces thymocyte apoptosis by blocking cell cycle progression, increasing intracellular calcium, and the Fas", FasL pathway in vitro, 2016, pp.44, 88~97
- Horinaka M, "Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells", Oncogene, 24, pp.7180~7189 (2005)
- Zeng L, "Death receptor 6 induces apoptosis not through type I or type II pathways, but via a unique mitochondria-dependent pathway by interacting with Bax protein", J. Biol. Chem, 287, pp.29125~29133 (2012)