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Anticancer activity, apoptosis and a structure-activity analysis of a series of 1,4-naphthoquinone-2,3-bis-sulfides.
Investigational New Drugs 2019 April 28
We have previously reported on the synthesis of 1,4-naphthoquinone-sulfides and in this investigation we report on their anticancer activity against 6 human cancer cell lines to evaluate their cytostatic effects. The 1,4-naphthoquinone-2,3-bis-sulfides were most effective against melanoma (UACC62) (GI50 = 6.5-10 μM) and prostate (PC3) (GI50 = 5.51-8.53 μM) cancer cell lines. They exhibited better cytostatic effects than etoposide (GI50 = 0.56-36.62 μM), parthenolide (GI50 = 3.58-25.97 μM) and VK3 (GI50 = 3.41-22.59 μM) against several of the cancer cell lines. These compounds are generally more selective for cancer cells than for normal human lung fetal fibroblasts (WI-38). One compound produces ROS which results in breast (MCF7) cancer cell death caused by apoptosis as evidenced by caspase 3/7 activation. Apoptosis was found to occur by a mitochondrial pathway and not by cell cycle arrest. Gene expression studies showed that p53 (a tumour suppressor), Mdm-2 (a p53 regulator) and Bcl-2 (apoptosis inhibitor) were up-regulated during apoptosis induction. These results encourage further research for potential application in cancer chemotherapy.
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