Synthesis of novel dibenzoxanthene derivatives and observation of apoptosis in human hepatocellular cancer cells.

We have synthesized dibenzoxanthene derivatives 2a-2i via nucleophilic substitution of methoxyl group and evaluated underlying antitumor molecular mechanism of target compounds. Compounds showed high cytotoxic activities against BEL-7402, A549, HeLa and MG-63 cancer cells in the µM range. These compounds inhibited the cell growth of BEL-7402 cells at S or G2/M phase. The compounds 2a-2i also induced the apoptosis of BEL-7402 cells. In addition, compounds enhanced the level of intramolecular ROS and decreased the mitochondrial membrane potential. Western blot analysis showed caspase-3 were activated and the expression of Bcl-2 and Bcl-xl was down-regulated. According to given results, these dibenzoxanthenes exhibited a broad spectrum of antiproliferative effects on various tumors and therapeutic efficacy. Molecular mechanism indicated that induction of apoptosis was associated with DNA fragmentation, ROS generation, mitochondria dysfunction. Compounds induced apoptosis in BEL-7402 cells through the intrinsic ROS-mediated mitochondrial pathway.
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