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Protective effect of plaunotol against doxorubicin-induced renal cell death

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Abstract

In searching for a safe and effective compound to be used as a chemoprotective agent to prevent toxicity of the anthracyclin doxorubicin to renal cells, the present study demonstrated that plaunotol, a purified acyclic diterpene from Croton stellatopilosus Ohba, showed potential protection against doxorubicin-induced cell death in human proximal tubule cells. Treatment of renal cells with doxorubicin resulted in a significant decrease in viability of the cells, and we next proved that such toxicity was mainly due to apoptotic cell death. Pretreatment of the cells with plaunotol for at least 9 h prior to doxorubicin exposure improved the cells’ survival. Plaunotol was shown to up-regulate the anti-apoptotic myeloid cell leukemia-1 (Mcl-1) level whereas it had no effect on the Bcl-2 level. The reduction in Mcl-1 after doxorubicin treatment was shown to be closely associated with the toxic action of the drug, and the increase in Mcl-1 induced by plaunotol pretreatment was able to prevent cell death induced by doxorubicin. Furthermore, the protective effect of plaunotol was evaluated in human lung and melanoma cells. Results indicated that plaunotol had no significantly protective effect in human lung carcinoma cells, whereas it sensitized melanoma cells to drug-induced cell death.

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Acknowledgments

This research was financially supported by The Thailand Research Fund through The Royal Golden Jubilee for PhD program (grant no. 5.Q.CU/50/C.1). The authors thank Mr. Krich Rajprasit for proofreading.

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Authors and Affiliations

  1. Pharmaceutical Technology (International) Program, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Chatchai Chaotham

  2. Department of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Wanchai De-Eknamkul

  3. Department of Pharmacology and Physiology, Faculty of Pharmaceutical Sciences, Chulalongkorn University, Bangkok, 10330, Thailand

    Pithi Chanvorachote

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  1. Chatchai Chaotham
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  2. Wanchai De-Eknamkul
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  3. Pithi Chanvorachote
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Correspondence to Wanchai De-Eknamkul or Pithi Chanvorachote.

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Chaotham, C., De-Eknamkul, W. & Chanvorachote, P. Protective effect of plaunotol against doxorubicin-induced renal cell death. J Nat Med 67, 311–319 (2013). https://doi.org/10.1007/s11418-012-0683-6

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  • DOI: https://doi.org/10.1007/s11418-012-0683-6

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