Apoptosis Induced by Farnesyltransferase Inhibitor Manumycin in Human Hepatoma Cancer Cell Line HepG2

Objective:To investigate the antitumor effect of farnesyltransferase inhibitor Manumycin in human hepatoma cell line HepG2, and to clarify its probable mechanisms. Methods: The growth inhibitory effect of farnesyltransferase inhibitor Manumycin on human hepatoma cell line HepG2 was observed by using MTT assay, Cell apoptosis was analyzed using flow cytometry, agrose gel electrophoresis of DNA and fluorescent microscopy. The protein expression of bcl 2, p53, and bax affected by Manumycin were determined by Western blot. Results: Farnesyltransferase inhibitor Manumycin significantly inhibited cell growth of human hepatoma cell line HepG2 with IC50 value of 17.65±0.58 μmol/L. DNA Ladder appeared on the agarose gel. And a typical subdiploid peak before Phase G0/G1 was detected by flow cytometry. The rates of apoptosis were correlated with the concentration of Manumycin and time of action. HepG2 cells were blocked at Phase G2/M which was correlated with time of action. Expression level of p53 in HepG2 was elevated after treatment with Manumycin, while there was no change for bcl 2 protein and bax protein. Conclusion: Manumycin can induce apoptosis in HepG2 cells which was associated with increasing of p53, but not bcl 2 and bax.