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Medicina 2018, 54(3), 39; https://doi.org/10.3390/medicina54030039

Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells

1,2,* , 3
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1,2
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4
,
1,2
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1,2
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1,2
,
1,2
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5,*
1
Translational Medicine Research Institute, College of Medicine, Yangzhou University, Yangzhou 225001, China
2
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou 225001, China
3
People’s Hospital of Xinjiang Uygur Autonomous Region, Urumqi 830001, China
4
School of Life Science and Medicine, Dalian University of Technology, Panjin 124221, China
5
College of Clinical Medicine, Yangzhou University, Yangzhou 225001, China
*
Authors to whom correspondence should be addressed.
Received: 21 February 2018 / Revised: 29 April 2018 / Accepted: 28 May 2018 / Published: 30 May 2018
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Abstract

Background and Objective: Although triptolide was effective for prostate cancer (PCa), the mechanism is still unclear. Androgen receptor (AR) plays a large role in the development and progression of PCa, even after castration. The present study aimed at investigating the effects of triptolide on AR protein stability and the possible mechanism. Materials and Methods: By blocking protein synthesis with cycloheximide (CHX), the effect of triptolide on AR protein stability was investigated with western blot assay. The potential role of calpains in triptolide reduced AR protein stability was investigated with calpain inhibitor and Ca2+ chelator. Results: Triptolide down-regulated AR protein level when protein synthesis was blocked by CHX, demonstrating the decrease of AR protein stability. The AR protein level was restored when the cells were co-treated with triptolide and calpain inhibitor or Ca2+ chelator, indicating the important role of calpains. Conclusions: The results indicate that triptolide can activate calpain via promoting intracellular Ca2+ accumulation, and thus decrease the stability of AR protein, subsequently resulting in the breakdown of the AR protein in LNCaP cells. This work provides an experimental basis and evidence to elucidate the anti-PCa mechanisms of triptolide. View Full-Text
Keywords: triptolide; androgen receptor; calpain; protein stability triptolide; androgen receptor; calpain; protein stability
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Li, W.; Liu, B.-D.; Liao, K.; Liu, Y.; Wan, Z.-J.; Dong, Y.-F.; Cao, Q.-Q.; Zhu, Q.; Gu, X. Alteration of Androgen Receptor Protein Stability by Triptolide in LNCaP Cells. Medicina 2018, 54, 39.

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