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Updated: Feb 13, 2026

Stabilizing Hepatocellular Phenotype Using Optimized Synthetic Surfaces
Published on: September 26, 2014
Synthetic Dibenzoxanthene Derivatives Induce Apoptosis Through Mitochondrial Pathway in Human Hepatocellular Cancer
Zhi Jia1, Hui Hui Yang1, Yun-Jun Liu2,3
1College of Pharmacy, Guangdong Pharmaceutical University, Guangzhou, 510006, People's Republic of China.
Abstract:
A new series of dibenzoxanthenes 4a-4f were synthesized through the nucleophilic substitution and characterized by NMR and MS spectra. Their antitumor activity was screened by MTT assay. Compounds (except 4b and 4c) displayed strong growth inhibitory effects against chosen five tumor cells under light irradiation. The molecular mechanism of compound-induced cell apoptosis was investigated by AO/EB staining, comet assay, DCFH-DA, JC-1 fluorescent probe, and western blotting. Compounds induced the apoptosis of HepG2 cells and DNA damage. Location assay showed that compounds entered the nucleus of tumor cells. Furthermore, it was found that compounds induced loss of mitochondrial membrane potential, acceleration of ROS production, and activation of caspse-3, caspase-7, and caspase-9 proteins. Compounds upregulated the expression of pro-apoptotic Bim and Bax and downregulated the expression of anti-apoptotic Bcl-xl and Bcl-2. These results indicated that compounds induced the apoptosis of HepG2 cells through ROS-mediated mitochondrial pathway. The induction of apoptosis by dibenzoxanthenes may provide an important mechanism for their cancer chemopreventive function.
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