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Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells

Medical Oncology volume 28, pages 307–314 (2011)Cite this article

Abstract

Curcumol isolated from Rhizoma Curcumae, a common traditional Chinese medicine, has been reported to possess antitumor effects, but little is known about the molecular mechanism. The current study tried to explore the molecular mechanism of curcumol-induced cell death in human lung adenocarcinoma (ASTC-a-1) cells. Cell counting kit (CCK-8) assay, fluorescence resonance energy transfer (FRET), confocal fluorescence microscopy imaging, emission spectral analysis, and flow cytometry (FCM) technologies were used to assess the characteristics of curcumol-induced cell death. FCM analysis showed that curcumol induced G2/M phase arrest, nuclear fragmentation and phosphatidylserine externalization, implying that curcumol dominantly induced apoptotic cell death. Dynamical imaging showed that curcumol induced a rapid translocation of Bax from cytosol into mitochondria within 6 h, leading to a rapid dissipation of mitochondrial membrane potential (∆Ψm), implying that mitochondria play an important role in the curcumol-induced apoptosis. The fact that Z-VAD-fmk, a broad-spectrum inhibitor of caspases, did not reduce the curcumol-induced apoptosis showed that caspases were not involved in curcumol-induced apoptosis, which was further verified by monitoring the caspase-3 activation inside living cells stably expressing SCAT3, a FRET plasmid. Collectively, we for the first time demonstrated that curcumol induced cell death in a dominant apoptotic fashion via the caspases-independent mitochondrial pathway in ASTC-a-1 cells.

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Acknowledgments

We wish to thank Professor M. Miura for providing SCAT3 plasmid. This study was supported by the Program for Changjiang Scholars and Innovative Research Team in University (IRT0829) and the Natural Science Foundation of Guangdong Province (81510631010000031 and 9251063101000009).

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Affiliations

  1. MOE Key Libratory of Laser Life Science & Institute of Laser Life Science, South China Normal University, 510631, Guangzhou, China

    Weiwei Zhang & Tongsheng Chen

  2. Joint Laboratory of Laser Oncology with Cancer Center of Sun Yat-sen University, South China Normal University, 510631, Guangzhou, China

    Weiwei Zhang & Tongsheng Chen

  3. School of Chinese Materia Medica, Guangzhou University of TCM, 510631, Guangzhou, China

    Zhiping Wang

Authors
  1. Weiwei Zhang
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  2. Zhiping Wang
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  3. Tongsheng Chen
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Corresponding author

Correspondence to Tongsheng Chen.

Additional information

Weiwei Zhang and Zhiping Wang contributed equally to this study.

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Zhang, W., Wang, Z. & Chen, T. Curcumol induces apoptosis via caspases-independent mitochondrial pathway in human lung adenocarcinoma ASTC-a-1 cells. Med Oncol 28, 307–314 (2011). https://doi.org/10.1007/s12032-010-9431-5

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  • DOI: https://doi.org/10.1007/s12032-010-9431-5

Keywords

  • Curcumol
  • Apoptosis
  • Caspases
  • Fluorescence resonance energy transfer (FRET)
  • Bax
  • Mitochondrial membrane potential (∆Ψm)