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Potential of piperine in modulation of voltage-gated K+ current and its influences on cell cycle arrest and apoptosis in human prostate cancer cells.
Eur Rev Med Pharmacol Sci. 2018 Dec;22(24):8999-9011
Authors: Ba Y, Malhotra A
Abstract
OBJECTIVE: Piperine is an attractive therapeutic alkaloid from black pepper that exhibits a broad spectrum of pharmacological properties over various pathological disorders including cancer. Voltage-gated K+ channels (KV) play an important role in regulating cancer cell proliferation and are considered as potential targets for the treatment of cancer. However, there is a paucity of information with regard to the implication of piperine in KV associated anticancer activities on human prostate cancer cells LNCaP and PC-3 cells. Therefore, the primary objective of the present study was to elucidate the anticancer action of piperine that might be mediated via voltage-gated K+ current (IK) blockade.
PATIENTS AND METHODS: Whole-cell patch clamp was used to record the modulatory effects of piperine on IK expressed in LNCaP and PC-3 cells. Moreover, the anticancer activity of piperine was evaluated by MTT assay, flow cytometry and live/dead assay.
RESULTS: Piperine significantly inhibited IK in a dose-dependent manner with an effective IC50 dose 39.91 µM in LNCaP and 49.45 µM in PC-3 cells. Also, piperine induced a positive shift in the relative activation curve in both cells. Blockade of IK by piperine exerted G0/G1 phase cell cycle arrest that led to inhibition of cell proliferation and induced apoptosis in a dose-dependent manner.
CONCLUSIONS: We showed that the anticancer effects of piperine are directly correlated with the blockade of IK in LNCaP and PC-3 cells. The study also confirmed that IK inhibition by piperine might be responsible for its anticancer activities in prostate cancer cells.
PMID: 30575945 [PubMed - in process]
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