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Capsaicin induces apoptosis in human osteosarcoma cells through AMPK-dependent and AMPK-independent signaling pathways

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Abstract

Recent studies have focused on the anti-tumor activity of capsaicin. However, the potential effects of capsaicin in osteosarcoma cells and the underlying mechanisms are not fully understood. In the current study, we observed that capsaicin-induced growth inhibition and apoptosis in cultured osteosarcoma cells (U2OS and MG63), which were associated with a significant AMP-activated protein kinase (AMPK) activation. AMPK inhibition by compound C or RNA interference suppressed capsaicin-induced cytotoxicity, while AMPK activators (AICAR and A769662) promoted osteosarcoma cell death. For the mechanism study, we found that AMPK activation was required for capsaicin-induced mTORC1 (mTOR complex 1) inhibition, B cell lymphoma 2 (Bcl-2) downregulation and Bax upregulation in MG63 cells. Capsaicin administration induced p53 activation, mitochondrial translocation and Bcl-2 killer association, such effects were dependent on AMPK activation. Interestingly, we observed a significant pro-apoptotic c-Jun NH2-terminal kinases activation by capsaicin in MG63 cells, which appeared to be AMPK independent. In conclusion, capsaicin possessed strong efficacy against human osteosarcoma cells. Molecular studies revealed that capsaicin activated AMPK-dependent and AMPK-independent signalings to mediate cell apoptosis. The results of this study should have significant translational relevance in managing this deadly malignancy.

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Abbreviations

MTT:

3-(4,5-Dimethyl-thiazol-2-yl)2,5-diphenyl tetrazolium bromide

AICAR:

5-Aminoimidazole-4-carboxamide riboside

ACC:

Acetyl-CoA carboxylase

AMPK:

AMP-activated protein kinase

mTORC1:

mTOR complex 1

Bak:

B-cell lymphoma 2 (Bcl-2) killer

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Acknowledgments

This work is supported by Discipline Leaders Project the Shanghai Municipal Pudong New District health system (PWRd2012-16) and Key Discipline Funding Project of Shanghai, Municipal Pudong New District Health Bureau (PWZxk2010-08).

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The authors have no conflict of interests.

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Authors and Affiliations

  1. Department of Orthopedics, Gongli Hospital of Pudong New District, No. 219, Miaopu Road, Pudong New District, Shanghai, 200135, China

    Hui Ying, Zhi Wang, Yan Zhang, Tie-yi Yang, Zhi-hong Ding, Shu-yi Liu, Jin Shao, Yue Liu & Xin-bing Fan

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  1. Hui Ying
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  2. Zhi Wang
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  3. Yan Zhang
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Correspondence to Yan Zhang.

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Hui Ying and Zhi Wang contributed equally to this paper.

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Ying, H., Wang, Z., Zhang, Y. et al. Capsaicin induces apoptosis in human osteosarcoma cells through AMPK-dependent and AMPK-independent signaling pathways. Mol Cell Biochem 384, 229–237 (2013). https://doi.org/10.1007/s11010-013-1802-8

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  • DOI: https://doi.org/10.1007/s11010-013-1802-8

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