Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Deltex E3 Ubiquitin Ligase 3L confers radioresistance in prostate cancer via Akt pathway

Junyi Xiang¹, Bodong Lv², Shufeng Fan¹, Zhitian Zhang¹, Hui Yang³

¹Department of Medical Imaging; ²Department of Urology Surgery, The Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou City. Zhejiang Province 310000; ³Department of Urology Surgery, Qianjiang Central Hospital of Chongqing, Chongqing City 409000, China.

For correspondence:- Hui Yang Email: HUYOKL87yh@163.com Tel:+8623979245641

Accepted: 25 June 2020 Published: 31 July 2020

Citation: Xiang J, Lv B, Fan S, Zhang Z, Yang H. Deltex E3 Ubiquitin Ligase 3L confers radioresistance in prostate cancer via Akt pathway. Trop J Pharm Res 2020; 19(7):1397-1402 doi: 10.4314/tjpr.v19i7.9

© 2020 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To determine the effect of Deltex E3 Ubiquitin Ligase 3L (DTX3L) on the radioresistance of prostate cancer (PCa).

Methods: A PCa cell model of radioresistance was established via exposure of cancer cell lines to fractionated radiation. The MTT {(3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide)} assay and western blotting were performed to evaluate the impact of DTX3L on cell survival and DNA damage repair. The molecular mechanism of action was evaluated by western blotting.

Results: DTX3L was elevated in PCa cell lines compared with normal primary prostate epithelial cells (p < 0.01). The survival of PCa cells exposed to radiation was promoted by overexpression of DTX3L, while knockdown of DTX3L abrogated the radioresistance. Moreover, overexpression of DTX3L decreased phosphorylation of histone H2AX (γH2AX) and increased Rad51 levels (p < 0.01). However, knockdown of DTX3L reversed the accumulation of γH2AX and Rad51. Phosphorylation of AKT was promoted by DTX3L overexpression, but was reduced by DTX3L knockdown (p < 0.01). Inhibition of AKT (protein kinase B) counteracted the promotion ability of DTX3L on the radioresistance of PCa cells via decreased cell survival ratio, and also inhibited DNA damage repair via accumulation of γ-H2AX and depletion of Rad51 (p < 0.01).

Conclusion: DTX3L increases the resistance of prostate cancer to radiotherapy and DNA damage repair in PCa via AKT pathway, indicating a potential therapeutic strategy to overcome radioresistance in PCa.

Keywords: DTX3L (Deltex E3 Ubiquitin Ligase 3L), DNA damage, Phosphorylation, Radioresistance, AKT, Protein kinase B, Prostate cancer