Journal of Nutrition and Health

The Korean Nutrition Society (한국영양학회)
권호 표지

Effect of [6] -Gingerol on Inhibition of Cell Proliferation in MDA-MB-231 Human Breast Cancer Cells

[6]-Gingerol이 인체 유방암세포인 MDA-MB-231의 세포증식 억제에 미치는 영향

  • Seo Eun-Young (Department of Food Science and Nutrition, Dankook University) ;
  • Lee Hyun-Sook (Department of Sports Science, Seoul Sports Graduate University) ;
  • Kim Woo-Kyung (Department of Food Science and Nutrition, Dankook University)
  • 서은영 (단국대학교 식품영양학과) ;
  • 이현숙 (서울스포츠대학원대학교, 스포츠과학과) ;
  • 김우경 (단국대학교 식품영양학과)
  • Published : 2005.10.01
Download PDF
⟨ Previous Next ⟩

Abstract

Ginger (Zingiber of oficinale Roscoe, Zingiberaceae) is one of the most frequently and heavily consumed dietary condiments throughout the world. Besides its extensive use as a spice, the rhizome of ginger has also been used in traditional oriental herbal medicine for the management of symptoms such as common cold, digestive disorders, rheumatism, neurologia, colic, and motion-sickness. The oleoresin from rhizomes of ginger contains [6] -gingerol (1- [4'-hydroxy-3'-methoxyphenyl]-5-hydroxy-3-decanone) and its homologs as pungent ingredients that have been found to possess many interesting pharmacological and physiological activities, such as anti-inflammatory, analgesic, antipyretic, antiheatotoxic, and cardiotonic effects. However, the effect of [6]-gingerol on cell proliferation in breast cancer cell are not currently well known. Therefore, in this study, we examined effect of [6]-gingerol on protein and mRNA expression associated with cell proliferation in MDA-MB-231 human breast. cancer cell lines. We cultured MDA-MB-231 cells in presence of 0, 2.5, 5 and $10{\mu}M$ of [6] -gingerol. [6]-Gingerol inhibited breast cancer cell growth in a dose-depenent manner as determined by MTT assay. ErbB2 and ErbB3 protein and mRNA expression were decreased dose-dependently in cells treated with [6]-gingerol (p<0.05). In addition, phosphorylated Akt levels and total hぉ levels were markedly decreased in cells treated with $2.5{\mu}M$ [6]-gingerol (p<0.05). In conclusion, we have shown that [6]-gingerol inhibits cell proliferation through ErbB2 and ErbB3, reduction in MDA-MB-231 human breast cancer cell lines.

Keywords

References

  1. Korea National Statistic Office. The Korean cause of death, 2002
  2. Huh KB. The present status of nutrition-related diseases and its countermeasures. Korean J Nutr 23(3): 197-207,1990
  3. Ryu YS. Astudy on dietary factor related to the incidence of breast cancer and of cervix cancer in Korean women. Master Thesis. Ewha Woman University, 1992
  4. Connell DW. The pungent principles of ginger and their importance in certain ginger products. Food Technol 11: 570-575, 1969
  5. Lewis YS, Mathew AG, Nambudiri ES, Krishnamburthy N. Oleoresin ginger. Flavour Ind 3: 78-81, 1972
  6. Mathew AG, Krishnamurthy N, Nambudiri ES, Lewis YS. Oil of ginger. Flavour Ind 4: 226-232, 1973
  7. Connell DW; Sutherland MD. A re-examination of gingerol, shogaol, and zingerone the pungent principle of ginger (Zingiber officinale Roscoe). Aust J Chem 22: 1033-1043, 1969 https://doi.org/10.1071/CH9691033
  8. Connell DW. The chemistry of the essential oil and oleoresin of ginger (Zingiber officinale Roscoe). Flavour Ind 1: 677-693, 1970
  9. Kang JH, Ahn BW, Lee DH, Byun HS, Kim SB, Park YH. Inhibitory effect of ginger and galic extracts on the DNA damage. Korean J Food Sci TechnoI 20(3): 287-292, 1988
  10. Katiyar SK. Inhibition of tumor promotion in sencar mouse skin by Zingiber officinale Rhizoma. Planta Med 56: 1023-1030, 1996
  11. Shin JH, Lee SJ, Sung NJ. Effect of Zingiber mioga, Zingiber mioga root, Zingiber officinale on lipid lipid concentation in hyperlipidemic rats. Korean J Soc Food Sci Nutr 31 (4): 679-684,2002
  12. Kim EJ, Ahn MS. Antioxidative effect of ginger extracts. Korean J Food Cookery Sci 9 (1) : 37-42, 1993
  13. Ji WD, Jeong HC, Lee SJ, Chun YG. Antimicrobial activity and distilled components of galic and ginger. J Agric Chem Biotechnol 40: 514-518, 1997
  14. Osborne CK, Hamilton B, Titus G, Livingston RB. Epidermal growth factor stimulation of human breast cancer cell in culture. Cancer Res 40: 2361-2366,1980
  15. Toi M, Nakamura T, Mukaida H, Wada T, Osaki A, Yamada H, Toge T, Niimoto M, Hattori T. Relation between epidermal growth factor receptor status and various prognostic factor in human breast cancer. Cancer 65 (9) : 1980-1984, 1990 https://doi.org/10.1002/1097-0142(19900501)65:9<1980::AID-CNCR2820650917>3.0.CO;2-U
  16. Lundy J, Schuss A, Stanick L, McCormack ES, Kramer S, Sorvillo JM. Expression of neu protein, epidermal growth factor receptor and transforming growth factor alpha in breast cancer, Correlation with clinicopathologic parameters. Am J Pathol 138 (6): 1527-1534, 1991
  17. Sporn MB, Todaro GJ. Auticrine secretion and malignant transformation of cells. N Eagle J Med 303: 878-880, 1980 https://doi.org/10.1056/NEJM198010093031511
  18. Sainsbury JRC, Farndon JR, Needham GK, Malcolm AJ, Harris AL. Epidermal growth factor receptor status as predictor of early recurrence of and death from breast cancer. Lancet 1: 1398-1402, 1987
  19. Spyratos F, Delarue JC, Andrieu C, Lidereau R, Champeme MH, Hacene K, Brunet M. Epidermal growth factor receptors and prognosis in primary breast cancer. Breast Cancer Res Treat 17 (2) : 83-89, 1990 https://doi.org/10.1007/BF01806288
  20. Lee EY, Surh YJ. Induction of apoptosis in HL-60 cells by pungent vanilloids, [6] -gingerol and [6] -paradol, Cancer Lett 134: 163-168, 1998 https://doi.org/10.1016/S0304-3835(98)00253-5
  21. Cross M, Dexter TM. Growth factors in development, transformation and tumorigenesis. Cell 64: 271-280, 1991 https://doi.org/10.1016/0092-8674(91)90638-F
  22. Liotta LA, Steeg P, Stetler-Stevenson W. Cancer metastasis and angiogenesis: An imbalance of positive and negative regulation. Cell 64: 327-336, 1991 https://doi.org/10.1016/0092-8674(91)90642-C
  23. Nicolson GL. Cancer progression and growth: Relationship of paracrine and autocrine growth mechanisms to organ preference metastasis. Exp Cell Res 204: 171-180, 1993 https://doi.org/10.1006/excr.1993.1022
  24. Hwang DL, Tay YC, Lin SS, Lev-Ran A. Expression of epidermal growth factor receptor in human lung tumors. Cancer 58: 2260-2272, 1986 https://doi.org/10.1002/1097-0142(19861115)58:10<2260::AID-CNCR2820581017>3.0.CO;2-U
  25. Carpenter G, Cohen S. Epidermal growth factor. Ann Rev Biochem 48: 193-197, 1979 https://doi.org/10.1146/annurev.bi.48.070179.001205
  26. Yarden Y, Sliwkowski MX. Untangling the ErbB signaling network. Natr Rev Mol Cell BioI 2: 127-137,2001 https://doi.org/10.1038/35052073
  27. Riese II DJ, Stem DF. Specificity within the EGF/ErbB receptor family signaling network. BioEssays 20: 41-48,1998 https://doi.org/10.1002/(SICI)1521-1878(199801)20:1<41::AID-BIES7>3.0.CO;2-V
  28. Olayioye MA, Neve RM, Lane HA, Hynes NE. The ErbB signaling network: receptor heterodimerization in development and cancer. EMBO J 19: 3159-3167,2000 https://doi.org/10.1093/emboj/19.13.3159
  29. Haeder M, Rotsch M, Bepler G, Henning C, Vemann KH, Heimann B, Moelling K. Epidermal growth factor receptor expression in human lung cancer cell line. Cancer Res 48: 1132-1140, 1988
  30. Torker A, Cantley LC. Signaling through the lipid products of phosphoinositide-3-OH kinase. Nature 387: 673-676,1997 https://doi.org/10.1038/42648
  31. Datta SR, Brunet A, Greenberg M. Cellular survival: a play in three Akts. Gene Dev 13: 2905-2927, 1999 https://doi.org/10.1101/gad.13.22.2905
  32. Squires MS, Hudson EA, Howells L, Sale S, Houghton CE, Jones JL, Fox LH, Dickens M, Prigent SA, Manson MM. Relevance of mitogene activated protein kinase (MARK) and phosphotidylinositol- 3-kinase/protein kinase B (PI3K/PKB) pathways to induction of apotosis by curcumin in breast cancer cells. Biochem ParmacoI 65(3): 361-376. 2003 https://doi.org/10.1016/S0006-2952(02)01517-4
  33. Hong RL, William HS, Hung MC. Curcumin inhibits tyrosine kinase activity of p185 and also deplets p185. Cancer Res 5: 1884-1891, 1999
  34. Mayo LD, Donner DB. Proc Natl Acad Sci USA 98: 11598-11603, 2001
  35. Cantley LC. The phosphoinositide 3-kinase family. Science 296: 1655-1657, 2002 https://doi.org/10.1126/science.296.5573.1655
  36. Lin J, Adam RM, Santiestevan E, Freeman MR. The phospholinositol 3-kinase pathway is a dominant growth factor activated cell survival pathway in LNCaP human prostate carcinoma cells. Cancer Res 59: 2891-2897,1999
  37. Burow ME, Weldon CB, Melnik LI, Duong BN, Collins-Burow BM, Beckman BS, McLachlan JA. P13-K/AKT regulation of NF-$\kappa$ B signaling events in suppression of TNF-linduced apoptosis. Biochem Biophys Res Commun 271: 342-345, 2000 https://doi.org/10.1006/bbrc.2000.2626
  38. Craen RJ, Lightfoot H, Cance WG. A decade of tyrosine kinases: from gene discovery to therapeutics. Surg Oncol 12: 39-50, 2003 https://doi.org/10.1016/S0960-7404(03)00004-5