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Kaempferol Suppresses Cisplatin-Induced Apoptosis Via Inductions of Heme Oxygenase-1 and Glutamate-Cysteine Ligase Catalytic Subunit in HEI-OC1 cells

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Abstract

Purpose

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.

Conclusion

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.

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Acknowledgments

This work was supported by the Korea Science and Engineering Foundation (KOSEF) through the Vestibulocochlear Research Center (VCRC) and the Biofoods Research Program, Ministry of Science & Technology.

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Authors and Affiliations

  1. Vestibulocochlear Research Center and Department of Biochemistry, School of Medicine, Wonkwang University, Chonbuk, 570-749, Republic of Korea

    Shang Shang Gao, Byung-Min Choi, Xiao Yan Chen, Ri Zhe Zhu, Youngho Kim & Bok-Ryang Kim

  2. Vestibulocochlear Research Center and Department of Microbiology, School of Medicine, Wonkwang University, Chonbuk, 570-749, Republic of Korea

    HongSeob So & Raekil Park

  3. Department of Biochemistry, College of Medicine, Kwandong University, Kangnung, 210-701, Republic of Korea

    Meesook Sung

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  1. Shang Shang Gao
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Gao, S.S., Choi, BM., Chen, X.Y. et al. Kaempferol Suppresses Cisplatin-Induced Apoptosis Via Inductions of Heme Oxygenase-1 and Glutamate-Cysteine Ligase Catalytic Subunit in HEI-OC1 cells. Pharm Res 27, 235–245 (2010). https://doi.org/10.1007/s11095-009-0003-3

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  • DOI: https://doi.org/10.1007/s11095-009-0003-3

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