International Journal of Oral Biology

The Korean Academy of Oral Biology (대한구강생물학회)
권호 표지
DOI QR코드

DOI QR Code

Apoptotic Effects of 6-Gingerol in Human Breast Cancer Cells

  • Kim, Hyun-Woo (Department of Pharmacology, Chonnam National University Medical School) ;
  • Oh, Deuk-Hee (Department of Pharmacology, Chonnam National University Medical School) ;
  • Koh, Jeong-Tae (Dental Science Research Institute and BK21 Project, School of Dentistry, Chonnam National University) ;
  • Lim, Young-Chai (Department of Pharmacology, Chonnam National University Medical School)
  • Received : 2015.12.14
  • Accepted : 2015.12.17
  • Published : 2015.12.31
Download PDF
⟨ Previous Next ⟩

Abstract

6-Gingerol exerts anti-tumor effects in various cancer cell models. We evaluated the effect of 6-gingerol on the growth of MCF-7 breast cancer cells and MCF-10A breast epithelial cells to determine whether any growth-inhibitory effects found were attributable to apoptosis, and to elucidate the underlying mechanism of action. 6-Gingerol inhibited the viability of both cell lines in a dose- and time-dependent manner; however, the degree of inhibition was greater in MCF-7 than MCF-10A cells. By flow cytometry, induction of dose- and time-dependent apoptosis was found, and the magnitude of apoptosis was also markedly greater in MCF-7 than MCF-10A cells. Expression of caspase-3 and poly (ADP-ribose) polymerase (PARP) was observed in MCF-7 cells treated with 6-gingerol, and further cleavage of PARP occurred in these cells. We suggest that 6-gingerol induces apoptosis in human breast cancer cells mainly by promoting caspase-3 expression and subsequent degradation of PARP.

Keywords

References

  1. Van der Wall RI, Buter J, Van der Waal I. Oral metastasis: report of 24 cases. Br J Oral Maxillofac Surg. 2003;41;3-6. doi:10.1016/S0266-4356(02)00301-7.
  2. Thorawat A, Naikmasur VG, Patil P, Perumal P. Secondary metastasis to mandible from breast carcinoma-a rare case report. J Clin Diagn Res. 2015;9:zd25-zd26. doi:10.7860/JCDR/2015/12986.6224.
  3. Grant KL, Lutz RB. Gingerol. Am J Health Syst Pharm. 2000;57:945-947.
  4. Surh YJ, Lee E, Lee JM. Chemoprotective properties of some pungent ingredients present in red pepper and ginger. Mutat Res. 1998;402:259-267. doi:10.1016/S0027-5107(97)00305-9.
  5. Kuo JM, Yeh DB, Pan BS. Rapid photometric assay evaluating antioxidative activity in edible plant material. J Agric Food Chem. 1999;47:3206-3209. doi:10.1021/jf981351o.
  6. Lantz RC, Chen GJ, Sarihan M, Solyom AM, Jolad SD, Timmermann BN. The effect of extracts from ginger rhizome on inflammatory mediator production. Phytomedicine. 2006;14:123-128. doi:10.1016/j.phymed.2006.03.003.
  7. Shukla Y, Singh M. Cancer preventive properties of ginger: a brief review. Food Chem Toxicol. 2007;45:683-690. doi:10.1016/j.fct.2006.11.002.
  8. Manju V, Nalini N. Chemopreventive efficacy of ginger, a naturally occurring anticarcinogen during the initiation, post-initiation stages of 1,2 dimethylhydrazine-induced colon cancer. Clin Chim Acta. 2005;358:60-67. doi:10.1016/j.cccn.2005.02.018.
  9. Suzuki F, Kobayashi M, Komatsu Y, Kato A, Pollard RB. A traditional Chinese herbal medicine, inhibits pulmonary metastasis of B16 melanoma. Anticancer Res. 1997;17:873-878.
  10. Park KK, Chun KS, Lee JM, Lee SS, Surh YJ. Inhibitory effects of [6]-gingerol, a major pungent principle of ginger, on phorbol ester-induced inflammation, epidermal ornithine decarboxylase activity and skin tumor promotion in ICR mice. Cancer Lett. 1998;129:139-144. doi:10.1016/S0304-3835(98)00081-0.
  11. Lee E, Surh YJ. Induction of apoptosis in HL-60 cells by pungent vanilloids, [6]-gingerol and [6]-paradol. Cancer Lett. 1998;134:163-168. doi:10.1016/S0304-3835(98)00253-5.
  12. Ishiguro K, Ando T, Maeda O, Ohmiya N, Niwa Y, Kadomatsu K, Goto H. Gingerol ingredients reduce viability of gastric cancer cells via distinct mechanisms. Biochem Biophys Res Commun. 2007;36:2218-2223. doi:10.1016/j.bbrc.2007.08.012.
  13. Shukla Y, Prasad S, Tripathi C, Singh M, George J, Kalra N. In vitro and in vivo modulation of testosterone mediated alterations in apoptosis reated proteins by 6-gingerol. Mol Nutr Food Res. 2007;51:1492-1502. doi: 10.1002/mnfr.200700197.
  14. Lee SH, Cekanova M, Baek SJ. Multiple mechanisms are involved in 6-gingerol induced cell growth arrest and apoptosis in human colorectal cancer cells. Mol Carcinog. 2008;47:197-208. doi:10.1002/mc.20374.
  15. Bray F, McCarron P, Parkin DM. The changing global patterns of female breast cancer incidence and mortality. Breast Can Res. 2004;6:229-239. doi:10.1186/bcr932.
  16. Yuan J, Horvitz HR. A first insight into molecular mechanisms of apoptosis. Cell. 2004;23:53-56.
  17. Koh DW, Dawson TM, Dawson VL. Mediation of cell death by poly(ADP-ribose) polymerase-1. Pharmacol Res. 2005;52:5-14. doi:10.1016/j.phrs.2005.02.011.
  18. Thangaiyan R, Liming W, Sipra B. Novel triterpenoid 25-hydroxy-3-oxoolean-12-en-28-oic acid induces growth arrest and apoptosis in breast cancer cells. Breast Can Res Treat. 2007;101:27-36. doi:10.1007/s10549-006-9275-z.
  19. Wojciechowski J, Horky M, Gueorguieva M, Wesierska-Gadek J. Rapid onest of nucleolar disintegration preceding cell cycle arrest in roscovitine-induced apoptosis of human MCF-7 breast cancer cells. Int J Cancer. 2003;106:486-495. doi:10.1002/ijc.11290.
  20. Deepali KH, Gerald AD, Teneille DW, Kara RJ, Xu D, Irene FN, David AG. Influence of p53 and caspase-3 activity on cell death and senescence in response to methotrexate in the breast tumor cell. Biochem Pharmacol. 2004;68:1699-1708. doi:10.1016/j.bcp.2004.06.033.
  21. Weinert TA, Hartwell LH. Characterization of RAD9 of Saccharomyces cerevisiae and evidence that its function acts posttranslationary in cell cycle arrest after DNA damage. Mol Cell Biol. 1990;10:6554-6564. https://doi.org/10.1128/MCB.10.12.6554
  22. O'onnor PM, Ferris DK, Pagano M, Draetta G, Pines J, Hunter T, Longo DL, Kohn KW. G2 delay induced by nitrogen mustard in human cells affects cyclin A/cdk2, and cyclin B1/cdc2-kinase complexes differently. J Biol Chem. 1993;268:8298-8303.
  23. Chisholm K, Bray BJ, Rosengren RJ. Tamoxifen and epigallocatechin gallate are synergistically cytotoxic to MDA-MB-231 human breast cancers cells. Anticancer Drugs. 2004;9:889-897.
  24. Al-Akoum M, Dodin S, Akoum A. Synergistic cytotoxic effects of tamoxifen and black cohosh on MCF-7 and MDA-MB-231 human breast cancer cells: an in vitro study. Can J Pharmacol. 2007;85:1153-1159. doi:10.1139/Y07-111.