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Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human hepatoma cells

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Abstract

Tanshinone IIA (Tan IIA), a natural product from herb Salvia miltiorrhiza Bunge, has potential anti-tumor activity. The aim of this study was to pinpoint the molecular mechanisms underlying Tan IIA-induced cancer cell apoptosis. Human hepatoma BEL-7402 cells treated with Tan IIA underwent assessment with MTT assay for cell viability, 10-day culture for colony formation, flow cytometry and fluorescence microscopy for apoptosis and cell cycle analysis. Changes in intracellular [Ca2+] and mitochondrial membrane potential (∆ψ) reflected the calcium-dependent apoptosis pathway. RT-PCR was used to detect gene expression of Bad and metallothionein 1A (MT 1A). Cytotoxicity of Tan IIA was tested in human amniotic mesenchymal stem cells (HAMCs). Tan IIA exhibited dose-dependent and time-dependent anticancer effects on BEL-7402 cells through apoptosis and G0/G1 arrest. Cells treated with Tan IIA increased their intracellular calcium, decreased their mitochondrial membrane potential and induced Bad and MT 1A mRNA expression. No adverse effects of Tan IIA were found in HAMCs. In conclusion, these results indicate that Tan IIA-induced cancer cell apoptosis acts via activation of calcium-dependent apoptosis signaling pathways and upregulation of MT 1A expression.

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Abbreviations

HAMCs:

Human amniotic mesenchymal stem cells

HCC:

Hepatocellular carcinoma

MT 1A:

Metallothionein 1A

SMB:

Salvia miltiorrhiza Bunge

Tan IIA:

Tanshinone IIA

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Acknowledgments

We thank Dr Li-Mei Yu at the Key Laboratory of Cell Engineering in Guizhou Province (Zunyi, China) for support and assistance in this study.

Conflict of interest

None.

Author information

Authors and Affiliations

  1. Department of Pharmacology, Pharmaceutical Institute of Guilin Medical University, 541004, Guilin, China

    Zhi-Kai Dai, Jiao-E Huang & Qing Xu

  2. Key Laboratory for the Chemistry and Molecular Engineering of Medicinal Resources of State Education Ministry, College of Chemistry and Chemical Engineering, Guangxi Normal University, 541004, Guilin, China

    Jiang-Ke Qin

  3. Department of Neurology, Aerospace Hospital of Guizhou, 563000, Zunyi, China

    Yong Luo

  4. Faculty of Basic Medicine, Guilin Medical University, North 2nd Huan Cheng Road, 541004, Guilin, China

    Hai-Lu Zhao

Authors
  1. Zhi-Kai Dai
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  2. Jiang-Ke Qin
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  3. Jiao-E Huang
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  4. Yong Luo
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  5. Qing Xu
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  6. Hai-Lu Zhao
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Corresponding author

Correspondence to Hai-Lu Zhao.

Additional information

Z.-K. Dai and J.-K. Qin contributed equally to this work.

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Dai, ZK., Qin, JK., Huang, JE. et al. Tanshinone IIA activates calcium-dependent apoptosis signaling pathway in human hepatoma cells. J Nat Med 66, 192–201 (2012). https://doi.org/10.1007/s11418-011-0576-0

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  • DOI: https://doi.org/10.1007/s11418-011-0576-0

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