Piperine, an alkaloid from black pepper, inhibits growth of human colon cancer cells via G1 arrest and apoptosis triggered by endoplasmic reticulum stress. Issue 10 (13th May 2014)

• Record Type: Journal Article
• Authors: Yaffe, Paul B.; Power Coombs, Melanie R.; Doucette, Carolyn D.; Walsh, Mark; Hoskin, David W.
• Is Part Of: Molecular carcinogenesis. Volume 54:Issue 10(2015:Oct.)
• Page Start: 1070
• Page End: 1085
• Publication Date: 2014-05-13
• Subjects: cytotoxicity -- caspase -- cell cycle -- phytochemical -- stress‐associated protein kinase; Carcinogenesis -- Molecular aspects -- Periodicals; 616.994071
• DOI: 10.1002/mc.22176
• Languages: English
• ISSNs: 0899-1987

Abstract

Abstract : Piperine, a piperidine alkaloid present in black pepper, inhibits the growth of cancer cells, although the mechanism of action is not well understood. In this study, we show that piperine (75–150 µM) inhibited the growth of several colon cancer cell lines but had little effect on the growth of normal fibroblasts and epithelial cells. Piperine inhibited HT‐29 colon carcinoma cell proliferation by causing G1 phase cell cycle arrest that was associated with decreased expression of cyclins D1 and D3 and their activating partner cyclin‐dependent kinases 4 and 6, as well as reduced phosphorylation of the retinoblastoma protein and up‐regulation of p21/WAF1 and p27/KIP1 expression. In addition, piperine caused hydroxyl radical production and apoptosis that was partially dependent on the production of reactive oxygen species. Piperine‐treated HT‐29 cells showed loss of mitochondrial membrane integrity and cleavage of poly (ADP‐ribose) polymerase‐1, as well as caspase activation and reduced apoptosis in the presence of the pan‐caspase inhibitor zVAD‐FMK. Increased expression of the endoplasmic reticulum stress‐associated proteins inositol‐requiring 1α protein, C/EBP homologous protein, and binding immunoglobulin protein, and activation of c‐Jun N‐terminal kinase and p38 mitogen‐activated protein kinase, as well as decreased phosphorylation of Akt and reduced survivin expression were also observed in piperine‐treated HT‐29 cells. Furthermore, piperine inhibited colony formation by HT‐29 cells, as well as the growth of HT‐29 spheroids. Cell cycle arrest and endoplasmic reticulum stress‐associated apoptosis following piperine treatment of HT‐29 cells provides the first evidence that piperine may be useful in the treatment of colon cancer. © 2014 Wiley Periodicals, Inc.