Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling

  • Authors:
    • Haitao Yin
    • Yun Zhou
    • Cuixia Wen
    • Chong Zhou
    • Wei Zhang
    • Xiang Hu
    • Lifeng Wang
    • Chuanwen You
    • Junfei Shao
  • View Affiliations

  • Published online on: July 18, 2014     https://doi.org/10.3892/or.2014.3342
  • Pages: 1610-1616
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Abstract

Temozolomide (TMZ), a DNA alkylating agent, represents the most important chemotherapeutic option for the treatment of glioblastoma in the clinic. Despite its frequent use, the therapeutic efficacy of TMZ remains very limited due to its frequent resistance in glioblastoma. Previous evidence suggested that curcumin (CUM), an ingredient of the Indian spice turmeric, is able to sensitize glioblastoma to TMZ treatment. However, the underlying molecular mechanism remains elusive. In the present study, we performed in vitro and in vivo experiments to evaluate the interaction of CUM and TMZ on the inhibition of glioblastoma and to investigate its potential mechanisms of action using U87MG cell lines and xenograft mouse models. We demonstrated that CUM enhanced the therapeutic response to TMZ in U87MG glioblastoma by enhancing apoptosis. We then proceeded to investigate the potential apoptotic signaling pathways that are involved. We observed a synergistic effect of the combination of CUM and TMZ in generating reactive oxygen species (ROS) production, suggesting that ROS may contribute to the impact of CUM on sensitizing TMZ treatment. We also showed that CUM and TMZ treatment alone significantly suppressed phosphorylated AKT and mTOR, whereas their combination achieved a more pronounced inhibitory effect. These data indicated that blockage of AKT/mTOR signaling appeared to contribute to the elevated apoptosis caused by the combination treatment with CUM and TMZ. In conclusion, this study provided molecular insights into the effects of CUM on the therapeutic response of glioblastoma to TMZ and opened new avenues for optimizing the therapeutic effects of TMZ-based therapies.
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October 2014
Volume 32 Issue 4

Print ISSN: 1021-335X
Online ISSN:1791-2431

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Spandidos Publications style
Yin H, Zhou Y, Wen C, Zhou C, Zhang W, Hu X, Wang L, You C and Shao J: Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncol Rep 32: 1610-1616, 2014.
APA
Yin, H., Zhou, Y., Wen, C., Zhou, C., Zhang, W., Hu, X. ... Shao, J. (2014). Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling. Oncology Reports, 32, 1610-1616. https://doi.org/10.3892/or.2014.3342
MLA
Yin, H., Zhou, Y., Wen, C., Zhou, C., Zhang, W., Hu, X., Wang, L., You, C., Shao, J."Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling". Oncology Reports 32.4 (2014): 1610-1616.
Chicago
Yin, H., Zhou, Y., Wen, C., Zhou, C., Zhang, W., Hu, X., Wang, L., You, C., Shao, J."Curcumin sensitizes glioblastoma to temozolomide by simultaneously generating ROS and disrupting AKT/mTOR signaling". Oncology Reports 32, no. 4 (2014): 1610-1616. https://doi.org/10.3892/or.2014.3342