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MMPT: a thiazolidin compound inhibits the growth of lung cancer H1792 cells via Fas-mediated and caspase-dependent apoptosis pathway

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Summary

MMPT, a thiazolidin compound, was identified in our laboratory as a novel antineoplastic agent with a broad spectrum of antitumor activity against many human cancer cells. However, the related mechanism has yet not been revealed. In this study, we investigated the cellular and molecular events underlying the antitumous function of this compound in human lung adenocarcinoma H1792 cells, focusing on the early cytotoxic effect. Treatment of H1792 cancer cells with MMPT (0.1–100 μM for 24–72 h) resulted in a growth inhibition in a dose and time-dependent manner, determined by MTT assay. This effect was accompanied by apoptosis, evidenced by Nucleosome ELISA, H33258 stained assay, and Sub-G1 analysis. Our data showed that MMPT caused activation of caspase-3, caspase-6 and caspase-8, but not caspase-9. The finding that MMPT induced apoptosis through a membrane-mediated mechanism was supported by the up-regulated expression of Fas (CD95/APO-1), and Fas ligand. Overall, our results demonstrated that MMPT induced growth inhibition of H1792 cells through a Fas-mediated and caspase-dependent apoptosis pathway, which suggested that MMPT might be used as a Fas/FasL and caspases promoter to initiate lung cancer cell apoptosis.

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Acknowledgments

This project was supported by the Doctoral Foundation of Shandong Province (2007BS02024), Natural Science Foundation of Shandong Province (Y2008D05) and the 11th Five-year Plan Provincial Key Construction of Qufu Normal University.

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Authors and Affiliations

  1. School of Life Science, Qufu Normal University, No.57 Jingxuan West Road, Qufu, 273165, China

    Yun-feng Zhao, Xiu-lan Li, Wen Niu, Zun-li Hu & Lin Lin

  2. School of chemistry and chemical engineering, Qufu Normal University, Qufu, China

    Yu-xi Sun

  3. School of Life Science, Shandong University, Jinan, 250100, China

    Qing-Zhong Kong

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  1. Yun-feng Zhao
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  2. Xiu-lan Li
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  4. Wen Niu
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  5. Zun-li Hu
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  6. Lin Lin
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  7. Qing-Zhong Kong
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Correspondence to Yun-feng Zhao.

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Zhao, Yf., Li, Xl., Sun, Yx. et al. MMPT: a thiazolidin compound inhibits the growth of lung cancer H1792 cells via Fas-mediated and caspase-dependent apoptosis pathway. Invest New Drugs 28, 318–325 (2010). https://doi.org/10.1007/s10637-009-9259-z

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  • DOI: https://doi.org/10.1007/s10637-009-9259-z

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