Piperine inhibits the proliferation of human prostate cancer cells via induction of cell cycle arrest and autophagy.
Piperine, an alkaloid from black and long peppers (Piper nigrum Linn & Piper longum Linn), has been reported to exhibit antitumor activities in vitro and in vivo. To further understand the antitumor mechanism of piperine, we investigated the growth inhibitory effects of piperine on human prostate cancer DU145, PC-3 and LNCaP cells. Piperine treatment resulted in a dose-dependent inhibition of the proliferation of these cell lines. Cell cycle arrest at G₀/G₁ was induced and cyclin D1 and cyclin A were downregulated upon piperine treatment. Notably, the level of p21(Cip1) and p27(Kip1) was increased dose-dependently by piperine treatment in both LNCaP and DU145 but not in PC-3 cells, in line with more robust cell cycle arrest in the former two cell lines than the latter one. Although piperine induced low levels of apoptosis, it promoted autophagy as evidenced by the increased level of LC3B-II and the formation of LC3B puncta in LNCaP and PC-3 cells. The piperine-induced autophagic flux was further confirmed by assaying LC3-II accumulation and LC3B puncta formation in the presence of chloroquine, a well-known autophagy inhibitor. Taken together, these results indicated that piperine exhibited anti-proliferative effect in human prostate cancer cells by inducing cell cycle arrest and autophagy.
Department of Immunobiology, Jinan University, Guangzhou 510632, China. Electronic address: dongyun1967@aliyun.com.
Dong-yun
DY
Ouyang
Long-hui
LH
Zeng
Hao
H
Pan
Li-hui
LH
Xu
Yao
Y
Wang
Kun-peng
KP
Liu
Xian-hui
XH
He
D000470:Alkaloids / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D052117:Benzodioxoles / Q000633:toxicity*; D059447:Cell Cycle Checkpoints / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D056750:Cyclin A1 / Q000235:genetics / Q000378:metabolism; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism; D050759:Cyclin-Dependent Kinase Inhibitor p21 / Q000235:genetics / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D016193:G1 Phase / Q000187:drug effects; D006801:Humans; D008297:Male; D010880:Piperidines / Q000633:toxicity*; D053284:Polyunsaturated Alkamides / Q000633:toxicity*; D011471:Prostatic Neoplasms / Q000378:metabolism / Q000473:pathology*; D015854:Up-Regulation
D000470:Alkaloids; D052117:Benzodioxoles; C503745:CCNA1 protein, human; C530104:CCND1 protein, human; C493956:CDKN1A protein, human; C436291:CDKN1B protein, human; D056750:Cyclin A1; D050759:Cyclin-Dependent Kinase Inhibitor p21; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; C008922:piperine
Autophagy; Cell cycle arrest; Chloroquine; Piperine; Prostate cancer cells