Vol 41: Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKC without inhibiting Akt.Report as inadecuate



 Vol 41: Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKC without inhibiting Akt.


Vol 41: Wedelolactone, a medicinal plant-derived coumestan, induces caspase-dependent apoptosis in prostate cancer cells via downregulation of PKC without inhibiting Akt. - Download this document for free, or read online. Document in PDF available to download.

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This article is from International Journal of Oncology, volume 41.AbstractEmerging studies indicate that metabolism of arachidonic acid through the 5-lipoxygenase 5-Lox pathway plays a critical role in the survival of prostate cancer cells raising the possibility that 5-Lox can be targeted for an effective therapy of prostate cancer. Wedelolactone WDL, a medicinal plant-derived natural compound, is known to inhibit 5-Lox activity in neutrophils. However, its effect on apoptosis in prostate cancer cells has not been addressed. Thus, we tested the effects of WDL on human prostate cancer cells in vitro. We observed that WDL kills both androgen-sensitive as well as androgen-independent prostate cancer cells in a dose-dependent manner by dramatically inducing apoptosis. We also found that WDL-induced apoptosis in prostate cancer cells is dependent on c-Jun N-terminal Kinase c-JNK and caspase-3. Interestingly, WDL triggers apoptosis in prostate cancer cells via downregulation of protein kinase Cε PKCε, but without inhibition of Akt. WDL does not affect the viability of normal prostate epithelial cells PrEC at doses that kill prostate cancer cells, and WDL-induced apoptosis is effectively prevented by 5-oxoETE, a metabolite of 5-Lox but not by 15-oxoETE, a metabolite of 15-Lox, suggesting that the apoptosis-inducing effect of WDL in prostate cancer cells is mediated via inhibition of 5-Lox activity. These findings indicate that WDL selectivity induces caspase-dependent apoptosis in prostate cancer cells via a novel mechanism involving inhibition of PKCε without affecting Akt and suggest that WDL may emerge as a novel therapeutic agent against clinical prostate cancer in human.



Author: SARVESWARAN, SIVALOKANATHAN; GAUTAM, SUBHASH C.; GHOSH, JAGADANANDA

Source: https://archive.org/



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