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JWA enhances As2O3-induced tubulin polymerization and apoptosis via p38 in HeLa and MCF-7 cells

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Abstract

Arsenic trioxide (As2O3) has potential anti-cancer activity against a wide range of carcinomas via apoptosis induction or oncoprotein degradation. The mechanisms involved are not fully elucidated. Here, we demonstrated that As2O3 induced-apoptosis in HeLa and MCF-7 cancer cells was in part triggered by tubulin polymerization. High expression of JWA promoted tubulin polymerization and increased the sensitivity of the cancer cells to As2O3. The activation of the p38 MAPK (mitogen-activated protein kinases) signaling pathway was found to contribute to JWA-promoted tubulin polymerization. Our results suggest that JWA may serve as an effective enhancer of microtubule-targeted As2O3 anti-cancer therapy.

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Acknowledgments

We are grateful to Dr. Jiahuai Han of the Scripps Research Institute, La Jolla, CA, USA and Dr. Gang Li of the University of British Columbia, Canada for providing pcDNA3-MKK6b and FLAG-JWA, respectively. This study was supported in part by the project funded by the Priority Academic Program Development (PAPD) of Jiangsu Higher Education Institutions and the National Natural Science Foundation of China (30930080 to JZ; 30771828 to JY).

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Authors and Affiliations

  1. Department of Molecular Cell Biology & Toxicology, The Key Laboratory of Modern Toxicology, Ministry of Education and Department of Occupational Medicine and Environmental Health, School of Public Health, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Lianlian Shen, Wenxia Xu, Aiping Li, Jian Ye & Jianwei Zhou

  2. Jiangsu Key Lab of Cancer Biomarkers, Prevention and Treatment, Cancer Center, Nanjing Medical University, 140 Hanzhong Road, Nanjing, 210029, People’s Republic of China

    Lianlian Shen, Wenxia Xu, Aiping Li, Jian Ye & Jianwei Zhou

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  1. Lianlian Shen
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  2. Wenxia Xu
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  3. Aiping Li
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Correspondence to Jianwei Zhou.

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Shen, L., Xu, W., Li, A. et al. JWA enhances As2O3-induced tubulin polymerization and apoptosis via p38 in HeLa and MCF-7 cells. Apoptosis 16, 1177–1193 (2011). https://doi.org/10.1007/s10495-011-0637-6

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