Involvement of p53-Mediated Mitochondrial Stress in the Apoptosis Induced by Flavonoids Purified from Rhus verniciflua Stokes in Human Osteosarcoma Cells

  • Chung, Song-Woo (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Lee, Seung-Ah (Department of Nursing, Chonnam Techno College, Department of Bioactive Materials, Research Center of Bioactive Materials, Chonbuk National University) ;
  • Park, Jong-Sun (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Ryu, Kwon-Woo (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Jang, Mun-Ju (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Park, Song-Soo (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Lee, Choon-Bong (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Kim, Jong-Ghee (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Jeon, Young-Mi (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University) ;
  • Lee, Jeong-Chae (Laboratory of Cell Biology in Department of Orthodontins and Institute of Oral Bioscience, Chonbuk National University, Department of Bioactive Materials, Research Center of Bioactive Materials, Chonbuk National University)
  • 발행 : 2007.03.31

초록

Dietary flavonoids have antioxidant and antitumor promoting effects. Rhus verniciflua Stokes (RVS) is a flavonoid-rich herbal medicine and has long been used as a food additive and an antitumor agent in Korea. Previous study demonstrated that a purified flavonoid fraction prepared from RVS, herein named RCMF (the RVS chloroform-methanol fraction), exhibited growth inhibition and induced apoptosis in human osteosarcoma(HOS) cells. This study evaluated if p53-mediated pathway is associated with the RCMF-induced apoptosis in HOS cells. RCMF was shown to be capable of inducing apoptosis of the cells, as expected, and transparently increased p53 expression in the cells. However, the RCMF-induced cytotoxicity was suppressed by transfecting the cells with antisense p53 oligonucleotide, which also inhibited the decrease of Bcl-2 and the increase of Bax in mitochondria, and the release of cytochrome c into cytosol. This finding suggests that p53-mediated mitochondrial stress is required for RCMF-induced apoptosis in HOS cells.

키워드

참고문헌

  1. Bernhard, D., Schwaiger, W., Crazzolara, R., Tinhofer, I., and Csordas, A., Enhanced MTT-reducing activity under growth inhibition by resveratrol in CEM-C7H2 lymphocytic leukemia cells. Cancer Lett. 195, 193-199 (2003) https://doi.org/10.1016/S0304-3835(03)00157-5
  2. Bradford, M.M., A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal. Biochem. 72, 248-254 (1976) https://doi.org/10.1016/0003-2697(76)90527-3
  3. Caltagirone, S., Rossi, C., Poggi, A., Ranelletti, F.O., Natali, P.G., Brunetti, M., Aiello, F.B., and Piantelli, M., Flavonoids apigenin and quercetin inhibit melanoma growth and metastatic potential. Int. J. Cancer 87, 595-600 (2000) https://doi.org/10.1002/1097-0215(20000815)87:4<595::AID-IJC21>3.0.CO;2-5
  4. Farr, D.R., Functional foods. Cancer Lett. 114, 59-63 (1997) https://doi.org/10.1016/S0304-3835(97)04626-0
  5. Gamet-Payrastre, L., Manenti, S., Gratacap, M.P., Tulliez, J., Chap, H., and Payrastre, B., Flavonoids and the inhibition of PKC and PI3-kinase. Gen. Pharmacol. 32, 279-286 (1999) https://doi.org/10.1016/S0306-3623(98)00220-1
  6. Gross, A., McDonnell, J.M., and Korsmeyer, S.J., BCL-2 family members and the mitochondria in apoptosis. Genes Dev. 13, 1899-1911 (1999) https://doi.org/10.1101/gad.13.15.1899
  7. Harris, C.C., Structure and function of the p53 tumor suppressor gene: clues for rational cancer therapeutic strategies. J. Natl. Cancer Inst. 88, 1442-1455 (1996) https://doi.org/10.1093/jnci/88.20.1442
  8. Harris, M.H. and Thompson, C.B., The role of the Bcl-2 family in the regulation of outer mitochondrial membrane permeability. Cell Death Differ. 7, 1182-1191 (2000) https://doi.org/10.1038/sj.cdd.4400781
  9. Jang, H.S., Kook, S.H., Son, Y.O., Kim, J.G., Jeon, Y.M., Jang, Y.S., Choi, K.C., Kim, J., Han, S.K., Lee, K.Y., Park, B.K., Cho, N.P., and Lee, J.C., Flavonoids purified from Rhus verniciflua Stokes actively inhibit cell growth and induce apoptosis in human osteosarcoma cells. Biochim. Biophys. Acta. 1726, 309-316 (2005) https://doi.org/10.1016/j.bbagen.2005.08.010
  10. Lee, J.C., Kim, J., Park, J.K., Chung, G.H., and Jang, Y.S., The antioxidant, rather than prooxidant, activities of quercetin on normal cells: quercetin protects mouse thymocytes from glucose oxidase-mediated apoptosis. Exp. Cell Res. 291, 386-397 (2003) https://doi.org/10.1016/S0014-4827(03)00410-5
  11. Lee, J.C., Lee, K.Y., Kim, J., Na, C.S., Jung, N.C., Chung, G.H., and Jang, Y.S., Extract from Rhus verniciflua Stokes is capable of inhibiting the growth of human lymphoma cells. Food Chem. Toxicol. 42, 1383-1388 (2004) https://doi.org/10.1016/j.fct.2004.03.012
  12. Li, L.Y., Luo, X., and Wang, X., Endonuclease G is an apoptotic DNase when released from mitochondria. Nature 412, 95-99 (2001) https://doi.org/10.1038/35083620
  13. Lowe, S.W., Ruley, H.E., Jacks, T., and Housman, D.E., p53-dependent apoptosis modulates the cytotoxicity of anticancer agents. Cell 74, 957-967 (1993) https://doi.org/10.1016/0092-8674(93)90719-7
  14. Maulik, N., Sato, M., Price, B.D., and Das, D.K., An essential role of NF-kappaB in tyrosine kinase signaling of p38 MAP kinase regulation of myocardial adaptation to ischemia. FEBS Lett. 429, 365-369 (1998) https://doi.org/10.1016/S0014-5793(98)00632-2
  15. Miranda, C.L., Stevens, J.F., Helmrich, A., Henderson, M.C., Rodriguez, R.J., Yang, Y.H., Deinzer, M.L., Barnes, D.W., and Buhler, D.R., Antiproliferative and cytotoxic effects of prenylated flavonoids from hops (Humulus lupulus) in human cancer cell lines. Food Chem. Toxicol. 37, 271-285 (1999) https://doi.org/10.1016/S0278-6915(99)00019-8
  16. Miyashita, T. and Reed, J.C., Tumor suppressor p53 is a direct transcriptional activator of the human bax gene. Cell 80, 293-299 (1995) https://doi.org/10.1016/0092-8674(95)90412-3
  17. Mukherjee, A.K., Basu, S., Sarkar, N., and Ghosh, A.C., Advances in cancer therapy with plant-based natural products. Curr. Med Chem. 8, 1467-1486 (2001) https://doi.org/10.2174/0929867013372094
  18. Muller, M., Wilder, S., Bannasch, D., Israeli, D., Lehlbach, K., Li-Weber, M., Friedman, S.L., Galle, P.R., Stremmel, W., Oren, M., and Krammer, P.H., p53 activates the CD95 (APO-1/Fas) gene in response to DNA damage by anticancer drugs. J. Exp. Med. 188, 2033-2045 (1998) https://doi.org/10.1084/jem.188.11.2033
  19. Pezutto, J.M., Plant-derived anticancer agents. Biochem. Pharmacol. 53, 121-133 (1997) https://doi.org/10.1016/S0006-2952(96)00654-5
  20. Son, Y.O., Lee, K.Y., Lee, J.C., Jang, H.S., Kim, J.G., Jeon, Y.M., and Jang, Y.S., Selective antiproliferative and apoptotic effects of flavonoids purified from Rhus verniciflua Stokes on normal versus transformed hepatic cell lines. Toxical. Lett. 155, 115-125 (2005) https://doi.org/10.1016/j.toxlet.2004.09.003
  21. Yang, E.B., Zhang, K., Cheng, L.Y., and Mack, P., Butein, a specific protein tyrosine kinase inhibitor. Biochem. Biophys. Res. Commun. 245, 435-438 (1998) https://doi.org/10.1006/bbrc.1998.8452
  22. Zanna, C., Ghelli, A., Porcelli, A.M., Martinuzzi, A., Carelli, V., and Rugolo, M., Caspase-independent death of Leber's hereditary optic neuropathy cybrids is driven by energetic failure and mediated by AIF and Endonuclease G. Apoptosis 10, 997-1007 (2005) https://doi.org/10.1007/s10495-005-0742-5