Increase of Bax/Bcl-X-L ratio and arrest of cell cycle by luteolin in immortalized human hepatoma cell line

摘要

Luteolin is a common constituent of many kinds of fruits and vegetables. It possesses the anti-neoplastic activities against several human cancers, but its activity against hepatocellular carcinoma (HCC) is seldom mentioned. To evaluate the activity against HCC and to provide information about the mechanism, we tested luteolin against five human hepatoma cell lines, namely HepG2, SK-Hep-1, PLC/PRF/5, Hep3B, and HA22T/VGH, with XTT assay and flow cytometry. The results showed that luteolin inhibited PLC/PRF/5, Hep3B and HA22/VGH at a concentration of 1 mug/ml, but it needed 5 mug/ml to inhibit HepG2 and 10 mug/ml for SK-Hep1 (P < 0.05). The inhibitive concentrations of 50% (IC50) of luteolin were between 7.29 mug/ml and 32.59 mug/ml, which were comparable with those of 5-FU (15.35 mug/ml to 32.84 mug/ml). The least effective cell line as affected by luteolin (SK-Hep1) was the most effective one when treating with 5-FU. The least effective cell line as affected by 5-FU (HA22T/VGH) was effectively affected by luteolin. It seemed that luteolin had some complementary activity to 5-FU against these HCC cell lines. The luteolin-treated PLC/PRF/5 cells exhibited typical changes of apoptosis with a characteristic DNA laddering pattern on gel electrophoresis. Luteolin also activated casepase-3, increased Bax. protein with a concomitant decrease in Bcl-X-L level. Increase in Bax/ Bcl-X-L ratio and activation of caspase-3 supported the apoptotic finding on gel electrophoresis. Luteolin also induced cell cycle arrest at G(0)/G(1) phase. We suggested that luteolin might exhibit anti-HCC activity as efficient as 5-FU by the mechanism of not only cell cycle arrest but also apoptosis. (C) 2004 Elsevier Inc. All rights reserved.