Selective Antiproliferative and Apoptotic Effects of Quercetin in Normal Versus Tumorigenic Hepatic Cell Lines

  • Jeon, Young-Mi (Lab. of Cell Biology in Department of Orthodontics and Institute of Oral Bioscience, Chonbuk National University) ;
  • Kim, Jong-Ghee (Lab. of Cell Biology in Department of Orthodontics and Institute of Oral Bioscience, Chonbuk National University) ;
  • Lee, Jeong-Chae (Lab. of Cell Biology in Department of Orthodontics and Institute of Oral Bioscience, Chonbuk National University)
  • Published : 2004.06.30

Abstract

Quercetin is a dietary anticancer chemical that is capable of inducing apoptosis in tumor cells. However, little is known about its biological effect in nonmalignant hepatic cells. Using embryonic normal hepatic cell line (BNL CL.2) and its SV40-transformed tumorigenic cell line (BNL SV A.8), we evaluated the effects of quercetin on cell proliferation and apoptosis. As the results, our present study demonstrated that quercetin had a selective growth inhibition in normal versus tumorigenic hepatic cells such that BNL SV A.8 cells were very sensitive to the quercetin-mediated cytotoxicity. In particular, as evidenced by the increased number of positively stained cells in the TUNEL assay, the induction of characteristic nuclear DNA ladders, and the migration of many cells to sub-G1 phase in the BNL SV A.8 cells, quercetin treatment more sensitively induced apoptosis in BNL SV A8 cells than in BNL CL.2 cells. Collectively, our findings suggest that quercetin can be approached as a potential agent that is capable of inducing selective growth inhibition and apoptosis of hepatic cancer cells.

Keywords

References

  1. Aligiannis, N., Mitaku, S., Mitrocotsa, D., and Leclerc, S., Flavonoids as cycline-dependent kinase inhibitors: Inhibition of cdc 25 phosphatase activity by flavonoids belonging to the quercetin and kaempferol series. Ptanta Med. 67, 468-470 (2001) https://doi.org/10.1055/s-2001-15807
  2. 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
  3. 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
  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, F., and Mukhtar, H., Selective growth-inhibitory, cell-cycle deregulatory and apoptotic response of apigenin in normal versus human prostate carcinoma cells. Biochem. Biophys. Res. Commun. 287, 914-920 (2001) https://doi.org/10.1006/bbrc.2001.5672
  8. Hollman, P.C. and Katan, M.B., Dietary Havonoids: intake, health effects and bioavailability. Food Chem. Toxicol. 37, 937-942 (1999) https://doi.org/10.1016/S0278-6915(99)00079-4
  9. 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
  10. Morel, I., Lescoat, G., Cogrel, P., Sergent, O., Pasdeloup, N., Brissot, P., Cillard, P., and Cillard, J., Antioxidant and iron-chelating activities of the flavonoids catechin, quercetin and diosmetin on iron-loaded rat hepatocyte cultures. Biochem. Pharmacol. 45, 13-19 (1993) https://doi.org/10.1016/0006-2952(93)90371-3
  11. 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
  12. 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
  13. Pezutto, J.M., Plant-derived anticancer agents. Biochem. Pharmacol. 53, 121-133 (1997)
  14. Plaumann, B., Fritsche, M., Rimpler, H., Brandner, G., and Hess, R.D., Flavonoids activate wild-type p53. Oncogene 13, 1605-1614 (1996)
  15. Smets, L.A., Programmed cell death (apoptosis) and response to anti-cancer drugs. Anti-Cancer Drugs 5, 3-9 (1994)
  16. 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
  17. 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