Kaempferol suppresses cisplatin-induced apoptosis via inductions of heme oxygenase-1 and glutamate-cysteine ligase catalytic subunit in HEI-OC1 cell.
OBJECTIVE
The present study was undertaken to elucidate the chemoprotective mechanism of kaempferol, which possesses anti-oxidative and anti-apoptotic properties.


METHODS
House Ear Institute-Organ of Corti 1 (HEI-OC1) cells were treated with kaempferol in the presence or absence of cisplatin. Cisplatin-induced oxidative stress was assessed by analysis of Comet assay, DNA-laddering assay and activation of caspases. Heme oxygenase-1 (HO-1), mitogen-activated protein kinase (MAPK) pathway and nuclear factor-E2-related factor 2 (Nrf2) were measured by Western blot analysis. Transfection of small interfering RNAs (siRNA), glutathione (GSH) assay and RT-PCR were performed in this study.


RESULTS
Kaempferol protected cells against cisplatin-induced apoptosis in a dose-dependent manner in HEI-OC1 cells. Kaempferol-induced HO-1 expression protected against cell death though the c-Jun N-terminal kinase (JNK) pathway and by the aid of Nrf2 translocation. Kaempferol increased the cellular level of GSH and the expression of GCLC time-dependently. siRNA GCLC blocked the increase of GSH level by kaempferol and the protective effect of kaempferol against cisplatin-induced cell death.


CONCLUSIONS
The expression of HO-1 by kaempferol inhibits cisplatin-induced apoptosis in HEI-OC1 cells, and the mechanism of protective effect is also associated with its inductive effect of GCLC expression.
Gao
Shang Shang
SS
Vestibulocochlear Research Center and Department of Biochemistry, School of Medicine, Wonkwang University, Chonbuk, 570-749, Republic of Korea.
Choi
Byung-Min
BM
Chen
Xiao Yan
XY
Zhu
Ri Zhe
RZ
Kim
Youngho
Y
So
HongSeob
H
Park
Raekil
R
Sung
Meesook
M
Kim
Bok-Ryang
BR
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D020134:Catalytic Domain / Q000187:drug effects / Q000235:genetics; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects / Q000235:genetics; D002945:Cisplatin / Q000037:antagonists & inhibitors / Q000633:toxicity*; D004305:Dose-Response Relationship, Drug; D004790:Enzyme Induction / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects; D005721:Glutamate-Cysteine Ligase / Q000096:biosynthesis* / Q000235:genetics; D051547:Heme Oxygenase-1 / Q000096:biosynthesis* / Q000235:genetics; D044949:Kaempferols / Q000502:physiology*; D051379:Mice; D009925:Organ of Corti / Q000166:cytology / Q000187:drug effects / Q000201:enzymology*
D044949:Kaempferols; C006552:kaempferol; D051547:Heme Oxygenase-1; D005721:Glutamate-Cysteine Ligase; D002945:Cisplatin