J Cancer 2020; 11(5):1115-1124. doi:10.7150/jca.36174 This issue

Research Paper

Dihydroartemisinin suppresses bladder cancer cell invasion and migration by regulating KDM3A and p21

Tao Wang*, Rongtuan Luo*, Wei Li, Houyu Yan, Shunqiang Xie, Wen Xiao, Yongfeng Wang, Bin Chen, Peide Bai, Jinchun Xing

The Key Laboratory of Urinary Tract Tumors and Calculi, Department of Urology Surgery, The First Affiliated Hospital, School of Medicine, Xiamen University, Xiamen, China 361003.
* These authors contributed equally to this work.

This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/). See http://ivyspring.com/terms for full terms and conditions.
Citation:
Wang T, Luo R, Li W, Yan H, Xie S, Xiao W, Wang Y, Chen B, Bai P, Xing J. Dihydroartemisinin suppresses bladder cancer cell invasion and migration by regulating KDM3A and p21. J Cancer 2020; 11(5):1115-1124. doi:10.7150/jca.36174. Available from https://www.jcancer.org/v11p1115.htm

File import instruction

Abstract

Emerging evidences have shown that Dihydroartemisinin (DHA), used in malaria treatment, possess anti-cancer activity. However, the study of its potential functional roles and the anti-cancer mechanisms in bladder cancer is limited. We performed this study to elucidate the influence of DHA in the biological behavior of bladder cancer cells and tried to explore the molecular mechanism. The results of CCK-8 assay showed that DHA significantly inhibited bladder cancer cell 5637, UMUC3 and T24 proliferation and the inhibitory effect is dose- and time- dependent. Further mechanism study showed that DHA performed its function via down-regulating the expression of histone demethylase KDM3A and inducing p21 expression. Moreover, wound healing and transwell migration/invasion assays revealed that DHA inhibited the ability of migration and metastasis in bladder cancer cell line T24. Finally, flow cytometry and colony formation assays demonstrated that DHA significantly promoted apoptosis of T24 cells and suppressed tumorigenesis as expected. Taken together, our study identifies the anti-cancer capacity of DHA in bladder cancer and explores the underlying mechanism.

Keywords: Dihydroartemisinin, bladder cancer, proliferation, migration, invasion, apoptosis, KDM3A