Piperine impairs cell cycle progression and causes reactive oxygen species-dependent apoptosis in rectal cancer cells.
Piperine, an alkaloid phytochemical found in the fruit of black and long pepper plants, is reported to inhibit the growth of cancer cells; however, the mechanism of action in human cancer cells is not clear. In this study we investigated the effect of piperine on the growth of HRT-18 human rectal adenocarcinoma cells. MTT assays showed that piperine inhibited the metabolic activity of HRT-18 cells in a dose- and time-dependent fashion, suggesting a cytostatic and/or cytotoxic effect. Flow cytometric analysis of Oregon Green 488-stained and propidium iodide-stained HRT-18 cells showed that piperine inhibited cell cycle progression. Piperine also caused HRT-18 cells to die by apoptosis, as determined by Annexin-V-FLUOS staining and characteristic changes in cell morphology. Flow cytometric analysis of dihydroethidium- and 2',7'-dichlorofluorescein diacetate-stained HRT-18 cells showed increased production of reactive oxygen species in piperine-treated cells. Furthermore, the antioxidant N-acetylcysteine reduced apoptosis in cultures of piperine-treated HRT-18 cells, indicating that piperine-induced cytotoxicity was mediated at least in part by reactive oxygen species. The cytostatic and cytotoxic effects of piperine on rectal cancer cells suggest that this dietary phytochemical may be useful in cancer treatment.
Department of Surgery, Dalhousie University, Halifax, Nova Scotia, Canada B3H 4R2.
Paul B
PB
Yaffe
Carolyn D
CD
Doucette
Mark
M
Walsh
David W
DW
Hoskin
D000111:Acetylcysteine / Q000494:pharmacology; D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D000470:Alkaloids / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D059447:Cell Cycle Checkpoints / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D065607:Cytochrome P-450 Enzyme Inhibitors; D016166:Free Radical Scavengers / Q000494:pharmacology; D006801:Humans; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D012004:Rectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D013385:Succinate Dehydrogenase / Q000378:metabolism
D000470:Alkaloids; D052117:Benzodioxoles; D065607:Cytochrome P-450 Enzyme Inhibitors; D016166:Free Radical Scavengers; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D017382:Reactive Oxygen Species; D013385:Succinate Dehydrogenase; C008922:piperine; D000111:Acetylcysteine