AI Article Synopsis
- - Hydroxamate compounds can kill cancer cells by generating reactive oxygen species (ROS), and this study modified lovastatin to include a hydroxamate core to enhance its effectiveness.
- - The new compounds showed increased ROS production compared to lovastatin, with compound 3c demonstrating the strongest activity against cancer cells, outperforming the chemotherapy drug cisplatin in prostate and breast cancer cell lines.
- - Compound 3c had lower toxicity on normal human cells, suggesting it is more selective for cancer cells, and its effectiveness is linked to its ability to generate ROS and activate certain cellular signaling pathways.
Article Abstract
Some hydroxamate compounds induce cancer cell death by intracellular reactive oxygen species (ROS). This study introduced the hydroxamate core into lovastatin, a fungus metabolite clinically used for the treatment of hypercholesterolemia. The resulting compounds were evaluated for the activity for inducing ROS production. Most compounds exhibited higher activity than original lovastatin. Of these compounds, compound 3c had the most potent activity. Test of cytotoxicity in a panel of human cancer cell lines indicated compound 3c had activities superior to cisplatin in prostate cancer PC-3 cells and breast cancer T47D cells. In contrast, it in amounts up to 40μM had a much lower cytotoxic effect on normal human IMR-90 cells. Further profiling of cell cycle progression, cell apoptosis, and DNA damage activated checkpoint signaling pathway revealed the important role of compound 3c-mediated cytotoxicity in ROS generation.
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| http://dx.doi.org/10.1016/j.bmcl.2016.10.005 | DOI Listing |
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