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Most conventional anticancer drugs exert either anti-proliferation or anti-angiogenesis activity. Recently, searching for potential multi-target agents has become an alternative strategy for cancer treatment. Several structurally different carbazole alkaloids from either natural or synthesized sources represent an important and heterogeneous class of anticancer agents. In the present study, we investigated the anticancer activity of a novel synthetic carbazole derivative, 9-[(6-chloropyridin-4-yl)methyl]-9H-carbazole-3-carbinol (HYL-6d), which is structurally different from other previously characterized carbazoles. HYL-6d-treated human breast cancer MCF-7 cells exhibited an increased population arrested at the sub-G1 and S phases, as well as an increase of p53 and decrease of cyclin D1, A and CDK2. Also, HYL-6d treatment induced MCF-7 cell apoptosis and this was accompanied by a decreased expression of Bcl-2, increased levels of p53 and Bcl-XS and the activation of caspase-9. Experimental results from human umbilical vascular endothelial cells (HUVECs) showed that HYL-6d also exerted its anti-angiogenic activity in HUVECs by inhibiting cell proliferation, migration, and tube formation induced by VEGF- or bFGF in vitro. In summary, the data indicate that HYL-6d exhibits both cytotoxic effects against human cancer cells and anti-angiogenic activities, which make it a potential therapeutic drug for cancer treatment.

Biological evaluation of 9-[(6-chloropyridin-4-yl)methyl]-9H-carbazole-3-carbinol as an anticancer agent