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Increased sensitivity of Hep G2 cells toward the cytotoxicity of cisplatin by the treatment of piper betel leaf extract

  • Molecular Toxicology
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Abstract

Piper betel leaves (PBL) are used in Chinese folk medicine for the treatment of various disorders. PBL has the biological capabilities of de-toxication, anti-oxidation and anti-mutation. In this study we first examined the effect of PBL extract on the activity of Glutathione S-transferase (GST) isoforms, and found that it inhibited total GST and the α class of GST (GSTA), but not the π class of GST (GSTP), and the μ class of GST (GSTM), activity in Hep G2 cells. RT-PCR results verified a reduction in the expression of GSTA1. Next, we examined whether PBL extract could increase the sensitivity of Hep G2 cells to anti-cancer drugs. The data showed that the cytotoxicity of cisplatin was significantly enhanced by the presence of PBL extract, accompanied by a reduction in the expression of multidrug resistance protein 2 (MRP2). These effects of PBL extract were compared to its major constitute, eugenol. Although eugenol decreased MRP2 level more effectively than PBL extract, it exhibited less sensitizing effect. In conclusion, we demonstrated that PBL extract was able to increase the sensitivity of Hep G2 cells to cisplatin via at least two mechanisms, reducing the expression of MRP2 and inhibiting the activity of total GST and the expression of GSTA. The data of this study support an application of PBL as an additive to reduce drug resistance.

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Abbreviations

CDNB:

1-Chloro-2,4-dinitrobenzene

GSH:

Glutathione

GST:

Glutathione S-transferase

MTT:

3-[4,5-dimethylthiazol-2-yl] 2,5-diphenyltetrazolium

MRP2:

Multidrug resistance protein 2

PBL:

Piper betel leaves

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Acknowledgements

This work was supported by the grants from National Science Council (NSC92-2745-B-040-001) and Chung Shan Medical University (CSMC 90-OM-B-007), Taichung, Taiwan.

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Authors and Affiliations

  1. Institute of Biochemistry and Biotechnology, Chung Shan Medical University, No 110, section 2, Chien Kauo N. Road, 402, Taichung, Taiwan

    Shun-Chieh Young, Chau-Jong Wang, Jui-Ling Hsu & Fen-Pi Chou

  2. Department of Pathology, Chung Shan Medical University Hospital, Taichung, Taiwan

    Jeng-Dong Hsu

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  1. Shun-Chieh Young
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  2. Chau-Jong Wang
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  3. Jeng-Dong Hsu
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  4. Jui-Ling Hsu
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  5. Fen-Pi Chou
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Correspondence to Fen-Pi Chou.

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Young, SC., Wang, CJ., Hsu, JD. et al. Increased sensitivity of Hep G2 cells toward the cytotoxicity of cisplatin by the treatment of piper betel leaf extract. Arch Toxicol 80, 319–327 (2006). https://doi.org/10.1007/s00204-005-0051-3

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  • DOI: https://doi.org/10.1007/s00204-005-0051-3

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