Apoptotic Effect of Vitisin A from Vitis Amurensis against MES-SA Uterine Cancer Cells

왕머루 포도에서 분리한 Vitisin A의 자궁암주에 대한 자멸사 효과

  • Lim, Jeong-Han (Graduate School of East-West Medical Science, Kyunghee University) ;
  • Lee, Hyo-Jeong (College of Oriental Medicine, Kyunghee University) ;
  • Lee, Eun-Ok (College of Oriental Medicine, Kyunghee University) ;
  • Lee, Hyo-Jung (College of Oriental Medicine, Kyunghee University) ;
  • Kwon, Hee-Young (College of Oriental Medicine, Kyunghee University) ;
  • Shim, Bum-Sang (College of Oriental Medicine, Kyunghee University) ;
  • Ahn, Kyoo-Seok (College of Oriental Medicine, Kyunghee University) ;
  • Kim, Sung-Hoon (Graduate School of East-West Medical Science, Kyunghee University, College of Oriental Medicine, Kyunghee University)
  • 임정한 (경희대학교 동서의학대학원) ;
  • 이효정 (경희대학교 한의과대학) ;
  • 이은옥 (경희대학교 한의과대학) ;
  • 이효정 (경희대학교 한의과대학) ;
  • 권희영 (경희대학교 한의과대학) ;
  • 심범상 (경희대학교 한의과대학) ;
  • 안규석 (경희대학교 한의과대학) ;
  • 김성훈 (경희대학교 동서의학대학원, 경희대학교 한의과대학)
  • Published : 2008.04.25

Abstract

The cytotoxic characteristics of Vitsin A isolated from Vitis amurensis L. were examined in human colorectal, breast, uterine and renal cancer cells. Vitsin A showed good cytotoxicity against various cancer cells with $IC_{50}$ of $1\;{\sim}\;30\;{\mu}M$. Among them, Vitisin A exhibited strongest cytotoxic effect against MES-SA cells with $IC_{50}$ of 1.11 ${\mu}M$ by SRB assay. To verify whether the cytotoxicity of Vitisin A may be associated with apoptosis, TdT-mediated-dUTP Nick-End Labeling (TUNEL) assay and cell cycle analysis were performed in MES-SA cells. Apoptotic bodies were observed in Vitisin A treated MES-SA cells by TUNEL assay. Also, Vitisin A effectively increased the portion of $sub-G_1$ DNA content by flow cytometric analysis. Taken together, these findings suggest that the cytotoxicity of Vitisin A against MES-SA cells is chiefly mediated by apoptosis.

Keywords

References

  1. 박재갑. 암정보, 국립암센터 출판부, pp 10-37, 2004
  2. Chen, K.G., Wang, Y.C., Schaner, M.E., Francisco, B., Duran, G.E., Juric, D., Huff, L.M., Padilla-Nash, H, Ried, T., Fojo, T., Sikic, B.I. Genetic and epigenetic modeling of the origins of multidrug-resistant cells in a human sarcoma cell line. Cancer Res. 65(20):9388-9397, 2005 https://doi.org/10.1158/0008-5472.CAN-04-4133
  3. Ozben, T. Mechanisms and strategies to overcome multiple drug resistance in cancer. FEBS Letters 580: 2903-2909, 2006 https://doi.org/10.1016/j.febslet.2006.02.020
  4. Robert, J., Jarry, C. Multidrug resistance reversal agents. J. Medicinal Chemistry 46(23):4805-4817, 2003 https://doi.org/10.1021/jm030183a
  5. Kaufmann, S.H., Hengartner, M.O. Programmed cell death: alive and well in the new millennium. Trends in Cell Biology 11: 526-534, 2001 https://doi.org/10.1016/S0962-8924(01)02173-0
  6. Kim, J.H., Kho, Y.H., Lee, H.J., Kim, M.R., Lee, S.M., Lee, H.Y. Regulation of apoptotic cell death in U937 leukemia cells by fatty acids. Food Sci. Biotechnol. 5: 539-542, 2001
  7. Kostakis, I.K., Tenta, R., Pouli, N., Marakos, P., Skaltsounis, A.L., Pratsinis, H., Kletsas, D. Design, synthesis, and antiproliferative activity of some novel aminosubstituted xanthenones, able to overcome multidrug resistance toward MES-SA/Dx5 cells. Bioorg. Med. Chem. Lett. 15(22):5057-5760, 2005 https://doi.org/10.1016/j.bmcl.2005.07.079
  8. Vaux, D.L. Toward an understanding of the molecular mechanisms of physiological cell death. Proc. Natl. Acad. Sci. 90: 786-789, 1993
  9. Garcia-Alonso, M., Rimbach, G., Rivas-Gonzalo, J.C., De Pascual-Teresa, S. Antioxidant and cellular activities of anthocyanins and their corresponding vitisins A studies in platelets, monocytes, and human endothelial cells. J. Agric. Food Chem. 52(11):3378-3384, 2004 https://doi.org/10.1021/jf035360v
  10. Huang, K.S., Lin, M., Cheng, G.F. Anti-inflammatory tetramers of resveratrol from the roots of Vitis amurensis and the conformations of the seven-membered ring in some oligostilbenes. Phytochemistry 58: 357-362, 2001 https://doi.org/10.1016/S0031-9422(01)00224-2
  11. Romero, C., Bakker, J. Interactions between grape anthocyanins and pyruvic acid, with effect of pH and acid concentration on anthocyanin composition and color in model solutions. J. Agric. Food Chem. 47(8):3130-3139, 1999 https://doi.org/10.1021/jf981286i
  12. Schwarz, M., Quast, P., von Baer, D., Winterhalter, P. Vitisin A content in Chilean wines from Vitis vinifera Cv. Cabernet Sauvignon and contribution to the color of aged red wines. J. Agric. Food Chem. 51(21):6261-6267, 2003 https://doi.org/10.1021/jf0346612
  13. Huang, Y.L., Tsai, W.J., Shen, C.C,, Chen, C.C. Resveratrol derivatives from the roots of Vitis thunbergii. J. Nat. Prod. 68(2):217-220, 2005 https://doi.org/10.1021/np049686p
  14. Jang, M.H., Piao, X.L., Kim, H.Y., Cho, E.J., Baek, S.H., Kwon, S.W., Park, J.H. Resveratrol oligomers from Vitis amurensis attenuate beta-amyloid-induced oxidative stress in PC12 cells. Biol. Pharm. Bull. 30(6):1130-1134, 2007 https://doi.org/10.1248/bpb.30.1130
  15. Lee, E.O., Lee, H.J., Hwang, H.S., Ahn, K.S., Chae, C.H., Kang, K.S., Lu, J.X., Kim, S.H. Potent inhibition of Lewis lung cancer growth by heyneanol A from the roots of Vitis amurensis through apoptotic and anti-angiogenic activities. Carcinogenesis 27(10):2059-2069, 2006 https://doi.org/10.1093/carcin/bgl055
  16. Morata, A., Gomez-Cordoves, M.C., Colomo, B., Suarez, J.A. Pyruvic acid and acetaldehyde production by different strains of Saccharomyces cerevisiae: relationship with Vitisin A and B formation in red wines. J. Agric. Food Chem. 51(25):7402-7409, 2003 https://doi.org/10.1021/jf0304167