Journal of Microbiology and Biotechnology

The Korean Society for Microbiology and Biotechnology (한국미생물·생명공학회)
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(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

  • Park, Chan-Woo (Department of Bioscience and Biotechnology, Konkuk University) ;
  • Song, Yong-Seok (Department of Ophthalmology and Visual Sciences, University of Wisconsin School of Medicine and Public Health) ;
  • Lee, Hee Pom (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Hong, Jin Tae (College of Pharmacy and Medical Research Center, Chungbuk National University) ;
  • Yoon, Do-Young (Department of Bioscience and Biotechnology, Konkuk University)
  • Received : 2017.03.27
  • Accepted : 2017.05.09
  • Published : 2017.07.28
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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.

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References

  1. Ferlay J, Soerjomataram I, Dikshit R, Eser S, Mathers C, Rebelo M, et al. 2015. Cancer incidence and mortality worldwide: sources, methods and major patterns in GLOBOCAN 2012. Int. J. Cancer 136: E359-E386. https://doi.org/10.1002/ijc.29210
  2. Wardak S. 2016. Human papillomavirus (HPV) and cervical cancer. Med. Dosw. Mikrobiol. 68: 73-84.
  3. Yim EK, Park JS. 2005. The role of HPV E6 a nd E 7 oncoproteins in HPV-associated cervical carcinogenesis. Cancer Res. Treat. 37: 319-324. https://doi.org/10.4143/crt.2005.37.6.319
  4. Kwon T, Bak Y, Ham SY, Yu DY, Yoon DY. 2016. A1E reduces stemness and self-renewal in HPV 16-positive cervical cancer stem cells. BMC Complement. Altern. Med. 16: 42.
  5. Elmore S. 2007. Apoptosis: a review of programmed cell death. Toxicol. Pathol. 35: 495-516. https://doi.org/10.1080/01926230701320337
  6. Ouyang L, Shi Z, Zhao S, Wang FT, Zhou TT, Liu B, Bao JK. 2012. Programmed cell death pathways in cancer: a review of apoptosis, autophagy and programmed necrosis. Cell Prolif. 45: 487-498. https://doi.org/10.1111/j.1365-2184.2012.00845.x
  7. Parrish AB, Freel CD, Kornbluth S. 2013. Cellular mechanisms controlling caspase activation and function. Cold Spring Harb Perspect. Biol. 5: a008672.
  8. Son DJ, Kim DH, Nah SS, Park MH, Lee HP, Han SB, et al. 2016. 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: 36852. https://doi.org/10.1038/srep36852
  9. Zheng J, Son DJ, Lee HL, Lee HP, Kim TH, Joo JH, et al. 2017. (E)-2-methoxy-4-(3-(4-methoxyphenyl)prop-1-en-1-yl)phenol suppresses ovarian cancer cell growth via inhibition of ERK and STAT3. Mol. Carcinog. DOI: 10.1002/mc.22648.
  10. Kim MS, Kim JH, B ak Y, Park YS, Lee DH, Kang JW, et al. 2012. 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. Nutr. Cancer 64: 1236-1244. https://doi.org/10.1080/01635581.2012.718405
  11. Cho S H, P ark MH, Lee HP, Back M K, S ung HC, Chang HW, et al. 2014. (E)-2,4-Bis(p-hydroxyphenyl)-2-butenal enhanced TRAIL-induced apoptosis in ovarian cancer cells through downregulation of NF-kappaB/STAT3 pathway. Arch. Pharm. Res. 37: 652-661. https://doi.org/10.1007/s12272-013-0326-9
  12. Lee US, Ban JO, Yeon ET, Lee HP, Udumula V, Ham YW, et al. 2012. 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. Biomol. Ther. (Seoul) 20: 538-543. https://doi.org/10.4062/biomolther.2012.20.6.538
  13. Kollipara PS, Jeong HS, Han SB, Hong JT. 2013. (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: 1471-1484. https://doi.org/10.1111/bph.12024
  14. Masters JR. 2002. HeLa cells 50 years on: the good, the bad and the ugly. Nat. Rev. Cancer 2: 315-319. https://doi.org/10.1038/nrc775
  15. Dini L, Coppola S, Ruzittu MT, Ghibelli L. 1996. Multiple pathways for apoptotic nuclear fragmentation. Exp. Cell Res. 223: 340-347. https://doi.org/10.1006/excr.1996.0089
  16. Marino G, Kroemer G. 2013. Mechanisms of apoptotic phosphatidylserine exposure. Cell Res. 23: 1247-1248. https://doi.org/10.1038/cr.2013.115
  17. Reutelingsperger CP, van Heerde WL. 1997. Annexin V, the regulator of phosphatidylserine-catalyzed inflammation and coagulation during apoptosis. Cell. Mol. Life Sci. 53: 527-532. https://doi.org/10.1007/s000180050067
  18. Pucci B, Kasten M, Giordano A. 2000. Cell cycle and apoptosis. Neoplasia 2: 291-299. https://doi.org/10.1038/sj.neo.7900101
  19. Chuang JY, Tsai YY, Chen SC, Hsieh TJ, Chung JG. 2005. Induction of G0/G1 arrest and apoptosis by 3-hydroxycinnamic acid in human cervix epithelial carcinoma (HeLa) cells. In Vivo 19: 683-688.
  20. Hsiao CJ, Hsiao G, Chen WL, Wang SW, Chiang CP, Liu LY, et al. 2014. Cephalochromin induces G0/G1 cell cycle arrest and apoptosis in A549 human non-small-cell lung cancer cells by inflicting mitochondrial disruption. J. Nat. Prod. 77: 758-765. https://doi.org/10.1021/np400517g
  21. Saralamma VV, Nagappan A, Hong GE, Lee HJ, Yumnam S, Raha S, et al. 2015. Poncirin induces apoptosis in AGS human gastric cancer cells through extrinsic apoptotic pathway by up-regulation of Fas ligand. Int. J. Mol. Sci. 16: 22676-22691. https://doi.org/10.3390/ijms160922676
  22. Kennedy RK, Naik PR, V eena V , Lak shmi B S, L ak shmi P , Krishna R, et al. 2015. 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: 71-82. https://doi.org/10.1016/j.cbi.2015.03.002
  23. Wang K, Zhang C, Bao J, Jia X, Liang Y, Wang X, et al. 2016. Synergistic chemopreventive effects of curcumin and berberine on human breast cancer cells through induction of apoptosis and autophagic cell death. Sci. Rep. 6: 26064. https://doi.org/10.1038/srep26064
  24. Fulda S, Debatin KM. 2006. Extrinsic versus intrinsic apoptosis pathways in anticancer chemotherapy. Oncogene 25: 4798-4811. https://doi.org/10.1038/sj.onc.1209608
  25. Taylor RC, Cullen SP, Martin SJ. 2008. Apoptosis: controlled demolition at the cellular level. Nat. Rev. Mol. Cell Biol. 9: 231-241. https://doi.org/10.1038/nrm2312
  26. Porter AG, Janicke RU. 1999. Emerging roles of caspase-3 in apoptosis. Cell Death Differ. 6: 99-104. https://doi.org/10.1038/sj.cdd.4400476
  27. Walczak H. 2013. Death receptor-ligand systems in cancer, cell death, and inflammation. Cold Spring Harb. Perspect. Biol. 5: a008698.
  28. Gao SY, Zhou XR, Gong TT, Jia LM, Li BX. 2016. Dibromoacetic acid induces thymocyte apoptosis by blocking cell cycle progression, increasing intracellular calcium, and the Fas/FasL pathway in vitro. Toxicol. Pathol. 44: 88-97. https://doi.org/10.1177/0192623315612939
  29. Horinaka M, Yoshida T, Shiraishi T, Nakata S, Wakada M, Nakanishi R, et al. 2005. Luteolin induces apoptosis via death receptor 5 upregulation in human malignant tumor cells. Oncogene 24: 7180-7189. https://doi.org/10.1038/sj.onc.1208874
  30. Zeng L, Li T, Xu DC, Liu J, Mao G, Cui MZ, et al. 2012. 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: 29125-29133. https://doi.org/10.1074/jbc.M112.362038

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