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Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits growth of human lung cancer A549 cells by arresting cell cycle and triggering apoptosis

  • Original Article
  • Lung Cancer
  • Published:
Chinese Journal of Cancer Research

Abstract

Objective

To examine the apoptotic effect of ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid (5F), a compound isolated from Pteris semipinnata L (PsL), in human lung cancer A549 cells.

Methods

A549 cells were treated with 5F (0–80 μg/ml) for different time periods. Cytotoxicity was examined using a MTT method. Cell cycle was examined using propidium iodide staining. Apoptosis was examined using Hoechst 33258 staining, enzyme-linked immunosorbent assay (ELISA) and caspase-3 activity analysis. Expression of representative apoptosis-related proteins was evaluated by Western blot analysis. Reactive oxygen species (ROS) level was measured using standard protocols. Potential interaction of 5F with cisplatin was also examined.

Results

5F inhibited the proliferation of A549 cells in a concentration- and time-dependent manner. 5F increased the accumulation of cells in sub-G1 phase and arrested the cells in the G2 phase. Exposure to 5F induced morphological changes and DNA fragmentation that are characteristic of apoptosis. The expression of p21 was increased. 5F exposure also increased Bax expression, release of cytochrome c and apoptosis inducing factor (AIF), and activation of caspase-3. 5F significantly sensitized the cells to cisplatin toxicity. Interestingly, treatment with 5F did not increase ROS, but reduced ROS production induced by cisplatin.

Conclusion

5F could inhibit the proliferation of A549 cells by arresting the cells in G2 phase and by inducing mitochondrial-mediated apoptosis.

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Authors and Affiliations

  1. Guangdong Key Laboratory for Research and Development of Natural Drugs, Guangdong Medical College, Zhanjiang, 524023, China

    Li Li, Ying-nian Lu, Yi Liu, Ke-feng Wu, Xian-ling Gong, Zhan-ping Gou & Nian-ci Liang

  2. Department of Surgery, the Chinese University of Hong Kong, New Territories, Hong Kong, China

    George G. Chen & Ming-yue Li

  3. Institute of Biochemistry and Molecular Biology, Guangdong Medical College, Zhanjiang, 524023, China

    Nian-ci Liang

Authors
  1. Li Li
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  2. George G. Chen
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  3. Ying-nian Lu
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  4. Yi Liu
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  5. Ke-feng Wu
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  6. Xian-ling Gong
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  9. Nian-ci Liang
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Corresponding authors

Correspondence to Li Li or Nian-ci Liang.

Additional information

This work was supported by the National Natural Science Foundation of China (No. 3987099), the Guangdong-Hong Kong Technology Cooperation Funding Scheme (No. GHP/022/06) and the Research Committee, Guangdong Medical College (No. XB0601).

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Li, L., Chen, G.G., Lu, Yn. et al. Ent-11α-hydroxy-15-oxo-kaur-16-en-19-oic-acid inhibits growth of human lung cancer A549 cells by arresting cell cycle and triggering apoptosis. Chin. J. Cancer Res. 24, 109–115 (2012). https://doi.org/10.1007/s11670-012-0109-8

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  • DOI: https://doi.org/10.1007/s11670-012-0109-8

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