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Kaempferol Induces Cell Death Through ERK and Akt-Dependent Down-Regulation of XIAP and Survivin in Human Glioma Cells

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Abstract

The present study was undertaken to determine the molecular mechanism by which kaempferol induces cell death in human glioma cells. Kaempferol resulted in loss of cell viability and inhibition of proliferation in a dose- and time-dependent manner, which were largely attributed to cell death. Kaempferol caused an increase in reactive oxygen species (ROS) generation and the kaempferol-induced cell death was prevented by antioxidants, suggesting that ROS generation is involved in kaempferol-induced cell death. Kaempferol caused depolarization of mitochondrial membrane potential. Western blot analysis showed that kaempferol treatment caused a rapid reduction in phosphorylation of extracellular signal-regulated kinase (ERK) and Akt. The ERK inhibitor U0126 and the Akt inhibitor LY984002 increased the kaempferol-induced cell death and overexpression of MEK, the upstream kinase of ERK, and Akt prevented the cell death. The expression of anti-apoptotic proteins XIAP and survivin was down-regulated by kaempferol and its effect was prevented by overexpression of MEK and Akt. Kaempferol induced activation of caspase-3 and kaempferol-induced cell death was prevented by caspase inhibitors. Taken together, these findings suggest that kaempferol results in human glioma cell death through caspase-dependent mechanisms involving down-regulation of XIAP and survivin regulating by ERK and Akt.

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Acknowledgement

This work was supported by the MRC program of MOST/KOSEF (R13-2005-009) in Korea.

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Authors and Affiliations

  1. Department of Oriental Medicine, Dongguk University, Kyung Ju, 780-714, South Korea

    Ji Cheon Jeong & Min Soo Kim

  2. Department of Physiology, College of Medicine, Pusan National University, Pusan, 602-739, South Korea

    Thae Hyun Kim & Yong Keun Kim

  3. MRC for ischemic tissue regeneration, College of Medicine, Pusan National University, Pusan, 602-739, South Korea

    Yong Keun Kim

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Jeong, J.C., Kim, M.S., Kim, T.H. et al. Kaempferol Induces Cell Death Through ERK and Akt-Dependent Down-Regulation of XIAP and Survivin in Human Glioma Cells. Neurochem Res 34, 991–1001 (2009). https://doi.org/10.1007/s11064-008-9868-5

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