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Anti-proliferative effect of 23,24-dihydrocucurbitacin F on human prostate cancer cells through induction of actin aggregation and cofilin-actin rod formation

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Abstract

Purpose

The cucurbitacins are a class of triterpenoid molecules that possess cytotoxic characteristics for plant defense against herbivore feeding. 23,24-dihydrocucurbitacin F (DHCF), a derivative of the cucurbitacin family, has been isolated as an active component from the root of Hemsleya amabilis (Cucurbitaceae), an ancient Chinese remedy for bacillary dysentery, gastroenteritis, and cancers. While the toxicity of other cucurbitacins has been explored in several cancers, little data exist on the effect of DHCF on human cancers, including prostate cancer (PCa). In this study, we explore the level and mechanisms of DHCF toxicity on human PCa cell lines.

Methods

Human PCa DU145, PC3, and LNCaP cells were treated with graded doses of DHCF in vitro, and anti-proliferative, cytotoxic, and proteomic effects were determined using MTS assay, cell cycle analysis, immunofluorescent staining, and western blotting.

Results

DHCF inhibited cell growth and induced cell cycle arrest at G2/M phase, formation of binucleated cells, and increased levels of apoptosis in all PCa cell lines tested. G-actin depletion, actin aggregation, and rod-like actin fibers, with little effect on microtubule structure, were observed after DHCF treatment. Actin aggregation and cofilin-actin rod formation were highly correlated with rapid and persistent dephosphorylation of cofilin-1 (cofilin). DHCF treatment resulted in upregulation of p21Cip1 and downregulation of cyclin A in all three PCa cell lines.

Conclusions

The anti-proliferative activity of DHCF on human PCa cells may be brought about by inducing actin aggregation and cofilin-actin rod formation, leading to cell cycle arrest, cytokinesis failure, and apoptosis.

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Acknowledgments

This study was supported by grants from the National Natural Science Foundation of China (No. 81173604), the Major State Basic Research Development Program of China (973 Program) (No. 2010CB833603) and the Specialized Research Program of “Twelfth Five-Year Plan” of China (No. 2011ZX09307-303-03).

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Authors and Affiliations

  1. Department of Immunobiology, Institute of Tissue Transplantation and Immunology, Jinan University, 601 Huangpu Dadao West, Guangzhou, 510632, China

    Shuai Ren, Dong-Yun Ouyang, Li-Hui Xu, Qing-Bing Zha & Xian-Hui He

  2. MSI, Essington, PA, 19029, USA

    Mark Saltis

  3. Department of Chemistry, Jinan University, Guangzhou, 510632, China

    Ji-Ye Cai

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  1. Shuai Ren
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  2. Dong-Yun Ouyang
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  4. Li-Hui Xu
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  5. Qing-Bing Zha
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  7. Xian-Hui He
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Correspondence to Xian-Hui He.

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Shuai Ren and Dong-Yun Ouyang contributed equally to this work.

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Ren, S., Ouyang, DY., Saltis, M. et al. Anti-proliferative effect of 23,24-dihydrocucurbitacin F on human prostate cancer cells through induction of actin aggregation and cofilin-actin rod formation. Cancer Chemother Pharmacol 70, 415–424 (2012). https://doi.org/10.1007/s00280-012-1921-z

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  • DOI: https://doi.org/10.1007/s00280-012-1921-z

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