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Original Articles

Tephrosin-induced autophagic cell death in A549 non-small cell lung cancer cells

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Pages 992-1000 | Received 15 Mar 2010, Accepted 31 Jul 2010, Published online: 08 Nov 2010
 

Abstract

Anticancer effect of tephrosin (1) has been documented; however, the molecular mechanisms underlying the cytotoxicity of tephrosin in cancer cells remain unclear. In the present paper, the proliferation inhibition rate of several cancer cells was tested using the MTT assay; cell cycle, reactive oxygen species (ROS), and mitochondrial membrane potential (MMP) were determined by flow cytometry; poly(ADP-ribose) polymerase (PARP) cleavage and heat shock protein 90 (Hsp90) expression were evaluated by Western blotting; autophagy was examined by confocal microscopy and light chain 3 (LC3) conversion assay. The results showed that exposure of the cells to tephrosin induced significant proliferation inhibition in a dose-dependent manner, especially on A549 with G2/M being arrested. Tephrosin was not found to induce cell apoptosis as PARP cleavage was not detected after 24 h treatment, but the formation of acidic vesicular organelle of autophagy character was found, and autophagy was further confirmed by the increase in the ratio of LC3-II to LC3-I. It was observed that tephrosin induced ROS generation and Hsp90 expression inhibition. These results indicate that tephrosin induces A549 cancer cell death via the autophagy pathway, and the roles of ROS generation and Hsp90 expression inhibition in this process need further study in the future.

Acknowledgements

This work was supported by the Natural Science Foundation of China (No. 30572314), the Basic Research Program of Science and Technology, Ministry of Science and Technology of China (2007FY210500), and the State Plan for High-Tech Research and Development of China (2007AA09Z405). We would like to thank Prof. Yucheng Gu from Syngenta Jealott's Hill International Research Centre for his proofreading and revision of the manuscript.

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