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DOI: 10.1055/s-0032-1321358
Potent NF-κB inhibitors from endophytic fungus of a taxus plant
NF-κB inhibitors isolated from natural sources that induce apoptosis are promising new anticancer agents. A potent NF-κB inhibitor (NFW9C-17) was isolated from an unidentified endophytic fungus of a Taxus plant from Pakistan named NFW9. The NF-κB inhibitory concentration (IC50) of NFW9C-17 was 0.20µg/mL (0.47µM) when using HeLa cells. Rocaglamide (IC50=0.075µM) was used as a positive control. The NF-κB inhibitory effect of NFW9C-17 is in agreement with previous literature reports. It is being further evaluated to uncover the mechanism through which it exhibits the attenuating effect on NF-κB. Three cancer cell lines, HT-29 colon cancer cells, HeLa cervical cells, and MDA-MB-231 hormone independent breast cancer cells, are being used to evaluate the effects of NFW9C-17. The observed effects have shown to be concentration dependent and the activity is comparable to the positive control, daunomycin, a potent chemotherapeutic agent. Our findings suggest that NFW9C-17 might be involved in the induction of apoptosis of treated cells. Evaluation of the biological activity of NFW9C-25, a new natural product analog from this species with NF-κB activity (IC50=0.7µg/mL; IC50=2.06µM), is ongoing to determine the structure activity relationship of both natural compounds.