Piperine protects cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells.
Piperine is a major component of black pepper, Piper nigrum Linn, used widely in traditional medicine. In this study, we examined whether piperine could protect House Ear Institute-Organ of Corti 1 (HEI-OC1) cells against cisplatin-induced apoptosis through the induction of heme oxygenase (HO)-1 expression. Piperine (10-100 microM) induced the expression of HO-1 in dose- and time-dependent manners. Piperine also induced antioxidant response element-luciferase and translocated nuclear factor-E2-related factor-2 (Nrf2) to nucleus. Piperine activated the c-Jun N-terminal kinase (JNK), extracellular signal-regulated kinase and p38 mitogen-activated protein kinase (MAPK) pathways, and the JNK pathway played an important role in piperine-induced HO-1 expression. Piperine protected the cells against cisplatin-induced apoptosis. The protective effect of piperine was abrogated by zinc protoporphyrin IX, an HO inhibitor, and antisense oligodeoxynucleotides against HO-1 gene. These results demonstrate that the expression of HO-1 by piperine is mediated by both JNK pathway and Nrf2, and the expression inhibits cisplatin-induced apoptosis in HEI-OC1 cells.
Choi
Byung-Min
BM
Department of Biochemistry, School of Medicine, Wonkwang University, Iksan, Chonbuk 570-749, Republic of Korea.
Kim
Sung-Min
SM
Park
Tae-Kwang
TK
Li
Guang
G
Hong
Sung-Jae
SJ
Park
Raekil
R
Chung
Hun-Taeg
HT
Kim
Bok-Ryang
BR
D000470:Alkaloids / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000633:toxicity*; D017209:Apoptosis / Q000187:drug effects*; D052117:Benzodioxoles / Q000494:pharmacology*; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D002945:Cisplatin / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D018072:Hair Cells, Auditory, Outer / Q000378:metabolism; D051547:Heme Oxygenase-1 / Q000378:metabolism*; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D051379:Mice; D051267:NF-E2-Related Factor 2 / Q000378:metabolism; D009925:Organ of Corti / Q000187:drug effects* / Q000201:enzymology; D010880:Piperidines / Q000494:pharmacology*; D053284:Polyunsaturated Alkamides / Q000494:pharmacology*; D015398:Signal Transduction; D014162:Transfection
D000470:Alkaloids; D000970:Antineoplastic Agents; D052117:Benzodioxoles; D051267:NF-E2-Related Factor 2; D010880:Piperidines; D053284:Polyunsaturated Alkamides; D051547:Heme Oxygenase-1; D048031:JNK Mitogen-Activated Protein Kinases; D002945:Cisplatin; C008922:piperine