Abstract
With the aim of discovering potential cytotoxic agents, a series of benzochromene derivatives were screened for their cytotoxic activity against seven human cancer cell lines by standard 3-(4, 5-dimethyl thiazol)-2,5-diphenyl tetrazolium bromide (MTT) assay. Apoptosis, as the mechanism of cell death, was investigated morphologically by acridine orange/ethidium bromide staining and cell surface expression assay of phosphatidylserine by Annexin V-PE/7-AAD technique. The effects of compounds on reactive oxygen species (ROS) and nitric oxide (NO) generations in three human breast cancer cell lines were also studied. All compounds showed significant cytotoxic activity with inhibitory concentration (IC50) values in the micromolar range (4.6-21.5 μM). The results of apoptosis evaluation suggested that the cytotoxic activity of these compounds in breast cancer cells occurs via apoptosis. MCF-7 cell line showed higher levels of ROS and NO production after treatment with compounds. The increase in ROS production after 4 and 24 h indicated that one of the ways that these compounds can induce apoptosis is by increasing ROS generation. Cytotoxic and apoptotic effects of these compounds in human cancer cells indicated that they can be a good candidate for further pharmacological studies to discover effective anticancer agents.
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