科研之友
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摘要
Diterpenes, present in many medicinal plants, have been the focus of continuous studies for the development of new anticancer agents. ZBB-006 is a new synthetic diterpenoid derivative which exhibited significant anti-proliferation activity against various cancer cell lines in our previous study. Here, we investigated the antitumor effect of ZBB-006 and its potential mechanisms in the human hepatocellular carcinoma cell line HepG2, both in vitro and in vivo. We found that oral administration of ZBB-006 effectively suppressed the growth of HepG2 xenograft tumor in nude mice without body weight decline, compared with the control group. Meanwhile, the growth inhibitory effect of ZBB-006 on HepG2 cells was observed with MTT assay. Then apoptosis induced by ZBB-006 in HepG2 cells was evidenced by DAPAPI staining and Annexin V/PI double staining assay. ZBB-006 also dissipated the mitochondrial membrane potential (Delta Psi m) apparently as revealed by JC-1 staining. Furthermore, the cleavage of PAPARP, activation of caspase-3 and caspase-9 but not caspase-8 was demonstrated by western blot assay both in vitro and in vivo. Additionally, the proapoptotic protein Bax was markedly elevated, while the antiapoptotic protein Bcl-2 was downregulated. Collectively, our data indicated that ZBB-006 exerted a strong antitumor effect on HepG2 cells by initiating the mitochondrial-dependent apoptosis, and it has potential to be explored as a new promising therapeutic agent against human hepatoma.
