Natural Product Sciences

The Korean Society of Pharmacognosy (한국생약학회)
권호 표지

Flavonoid Fraction Purified from Rhus verniciflua Stokes Actively Inhibits Cell Growth Via Induction of Apoptosis in Mouse Tumorigenic Hepatocytes

  • Lee, Jeong-Chae (Department of Orthodontics and Institute of Oral Bioscience, Chonbuk National University)
  • Published : 2004.04.30
Download PDF
⟨ Previous Next ⟩

Abstract

Dietary flavonoids are currently receiving considerable attention in developing novel cancer-preventive approaches because of their potential capacities to actively induce apoptosis of cancer cells. In our previous report, a flavonoid fraction, which consisted mainly of protocatechuic acid, fustin, fisetin, sulfuretin, and butein and named RCMF (RVS chloroform-methanol fraction), was prepared from a crude acetone extract of Rhus verniciflua Stokes (RVS) that is traditionally used as food additive and herbal medicine. In this study, we evaluated the effects of the RCMF on cell proliferation and apoptosis using SV40-transformed tumorigenic hepatocytes, BNL SV A.8. Tritium uptake assay showing the proliferative capacity of the cells was strongly suppressed in the presence of RCMF. This anti-proliferative effect was further confirmed through trypan blue exclusion. RCMF-mediated suppression of cell growth was verified to be apoptotic, based on the increase in DNA fragmentation, low fluorescence intensity in nuclei after propidium iodide staining, and the appearance of DNA laddering. Collectively, this study demonstrated that RCMF can be approached as a potential agent that is capable of significantly inhibiting cell growth of hepatic cancer cells.

Keywords

References

  1. 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
  2. Christou, L., Hatzimichael, E., Chaidos, A., Tsiara, S., and Bourantas, K.L., Treatment of plasma cell leukemia with vincristine, liposomal doxorubicin and dexamethasone. Eur. J. Haematol. 67,51-53 (2001) https://doi.org/10.1034/j.1600-0609.2001.067001051.x
  3. Duarte, J., Perez-Vizcaino, F., Zarzuelo, A., Jimenez, J., and Tamargo, J., Vasodilator effects of quercetin in isolated rat vascular smooth muscle. Eur. J. Pharmacol. 239, 1-7 (1993) https://doi.org/10.1016/0014-2999(93)90968-N
  4. Formica, J.V., and Regelson, W., Review of the biology of quercetin and related bioflavonoids. Food Chem. Toxicol. 33, 1061-1080 (1995) https://doi.org/10.1016/0278-6915(95)00077-1
  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. Gao, Z., Huang, K., Yang, X., and Xu, H., Free radical scavenging and antioxidant activities of flavonoids extracted from the radix of Scutellaria baicalensis Georgi. Biochim. Biophys. Acta 1472, 643-650 (1999) https://doi.org/10.1016/S0304-4165(99)00152-X
  7. Gupta, S., Afaq, P., and Mukhtar, H., Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in nonnal versus human prostate carcinoma cells. Biochem. Biophys. Res. Commun. 287, 914-920 (2001) https://doi.org/10.1006/bbrc.2001.5672
  8. Hong, D.H., Han, S.B., Lee, C.W, Park, S.H., Jeon, Y.J., Kim, M.J., Kwak, S.S., and Kim, H.M., Cytotoxicity of urushiols isolated from sap of Korean lacquer tree (Rhus verniciflua Stokes). Arch. Pharmacol. Res. 22, 638-641 (1999) https://doi.org/10.1007/BF02975339
  9. Jung, N.C., Biological activity of urushiol and flavonoids from Lac tree (Rhus verniciflua Stokes). Ph.D. thesis, Chonnam National University, Kwang-ju, South Korea (1998)
  10. Kim, l.W, Shin, D.H., and Baek, N.l., Identification of antioxidative components from ethanol extract of Rhus verniciflua Stokes. Kor. J. Food Sci. Technol. 31, 1654-1660 (1999)
  11. Kitts, D.D., and Lim, K.T., Antitumorigenic and cytotoxic properties of an ethanol extract derived from Rhus verniciflua Stokes (RVS). J. Toxicol. Env. Health 64, 357-371 (2001) https://doi.org/10.1080/152873901316981330
  12. Lee, J.C., Jung, H.Y, and Lim, K.T., Effects of Rhus verniciflua stokes (RVS) on the plasma level of cholesterol and tumor growth in mouse. J. Toxicol. Pub. Health 15,169-175 (1999)
  13. Lee, J.C., Kim, J., Lim, K.T., Yang, M.S., and Jang, Y.S., Ethanol eluted extract of Rhus verniciflua Stokes showed both antioxidant and cytotoxic effects on mouse thymocytes depending on the dose and time of the treatment. J. Biochem. Mol. Biol. 34, 250-258 (2001)
  14. Lee, J.C., Kim, J., and Jang, Y.S., Ethanoleluted extract of Rhus verniciflua Stokes inhibits cell growth and induces apoptosis in human lymphoma cells. J. Biochem. Mol. Biol. 36, 337-343 (2003) https://doi.org/10.5483/BMBRep.2003.36.4.337
  15. Lee, J.C., Kim, J., Park, J.K, Chung, G.H., and Jang, Y.S., The anti oxidant, rather than pro oxidant, activities of quercetin on nornal 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
  16. Lee, J.C., Lim, K.T., and Jang, Y.S., Identification of Rhus vemiciflua Stokes compounds that exhibit free radical scavenging and anti apoptotic properties. Biochim. Biophys. Acta 1570,181-191 (2002) https://doi.org/10.1016/S0304-4165(02)00196-4
  17. 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
  18. 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
  19. Paschka, A.G., Butler, R., and Young, C.Y.F., Induction of apoptosis in prostate cancer cell lines by the green tea component, (-)-epigallocatechin-3-gallate. Cancer Lett. 130, 1-7 (1998) https://doi.org/10.1016/S0304-3835(98)00084-6
  20. Pezutto, J.M., Plant derived anticancer agents. Biochem Pharmacol. 53, 121-133 (1997) https://doi.org/10.1016/S0006-2952(96)00654-5
  21. Plaumann, B., Fritsche, M., Rimpler, H., Brandner, G., and Hess, R.D., Flavonoids activate wild type p53. Oncogene 13, 1605-1614 (1996)
  22. Smets, L.A., Programmed cell death (apoptosis) and response to anti cancer drugs. Anti Cancer Drugs 5, 3-9 (1994)
  23. Whitmarsh, A.J., and Davis, R.J. Transcription factor AP-1 regulation by mitogen-activated protein kinase signal transduction pathways. J. Mol. Med. 74, 589-607(1996) https://doi.org/10.1007/s001090050063
  24. Wong, W.S., and McLean, A.E., Effects of phenolic antioxidants and flavonoids on DNA synthesis in rat liver, spleen, and testis in vitro. Toxicology 139, 243-253 (1999) https://doi.org/10.1016/S0300-483X(99)00136-5
  25. 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
  26. Yoshioka, K., Deng, T., Cavigelli, M., and Karin, M. Antitumor promotion by phenolic antioxidants: inhibition of AP-1 activity through induction of Fra expression. Proc. Natl. Acad. Sci. USA. 92, 4972-4976 (1995) https://doi.org/10.1073/pnas.92.11.4972
  27. Zhang, H.L., Nagatsu, A., Okuyama, H., Mizukami, H., and Sakakibara, J., Sesquiterpene glycosides from cotton oil cake. Phytochemistry 48, 665-668 (1998) https://doi.org/10.1016/S0031-9422(98)00075-2