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1344627 
Journal Article 
Piperine protects cisplatin-induced apoptosis via heme oxygenase-1 induction in auditory cells 
Choi, BMin; Kim, SMin; Park, TaeK; Li, G; Hong, SJae; Park, R; Chung, HunT; Kim, BokR 
2007 
1 
Journal of Nutritional Biochemistry
ISSN: 0955-2863
EISSN: 1873-4847 
18 
9 
615-622 
17418561 
WOS:000249035600006 
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 I (HET-OCI) cells against cisplatin-induced apoptosis
through the induction of heme oxygenase (HO)-1 expression. Piperine (10-100 mu M) induced the
expression of HO-I 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-I 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-I gene. These
results demonstrate that the expression of HO-I by piperine is mediated by both JNK pathway and
Nrf2, and the expression inhibits cisplatin-induced apoptosis in HEI-OCl cells. (c) 2007 Elsevier
Inc. All rights reserved. 
cisplatin; heme oxygenase; MAPK; Nrf2; piperine