Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Ying Zhang; Wei Wei; Changying Li; Siyuan Yan; Shanshan Wang; Shudong Xiao; Chenchen He; Jing Li; Zhi Qi; Benyi Li; Kuo Yang; Changlin Li

doi:10.1038/s41419-022-05490-5

Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Ying Zhang, Wei Wei, Changying Li, Siyuan Yan, Shanshan Wang, Shudong Xiao, Chenchen He, Jing Li, Zhi Qi, Benyi Li, Kuo Yang^*, Changlin Li^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

2 Citations (Scopus)

Abstract

Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.

Original language	English
Article number	1034
Journal	Cell Death and Disease
Volume	13
Issue number	12
DOIs	https://doi.org/10.1038/s41419-022-05490-5
Publication status	Published - Dec 2022
Externally published	Yes

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title = "Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein",

abstract = "Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.",

author = "Ying Zhang and Wei Wei and Changying Li and Siyuan Yan and Shanshan Wang and Shudong Xiao and Chenchen He and Jing Li and Zhi Qi and Benyi Li and Kuo Yang and Changlin Li",

note = "Publisher Copyright: {\textcopyright} 2022, The Author(s).",

year = "2022",

month = dec,

doi = "10.1038/s41419-022-05490-5",

language = "English",

volume = "13",

journal = "Cell Death and Disease",

issn = "2041-4889",

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TY - JOUR

T1 - Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

AU - Zhang, Ying

AU - Wei, Wei

AU - Li, Changying

AU - Yan, Siyuan

AU - Wang, Shanshan

AU - Xiao, Shudong

AU - He, Chenchen

AU - Li, Jing

AU - Qi, Zhi

AU - Li, Benyi

AU - Yang, Kuo

AU - Li, Changlin

PY - 2022/12

Y1 - 2022/12

N2 - Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.

AB - Although second-generation therapies like abiraterone (ABI) and enzalutamide (ENZ) benefit patients with castration-resistant prostate cancer (CRPC), drug resistance frequently occurs, eventually resulting in therapy failure. In this study, we used two libraries, FDA-approved drug library and CRISP/Cas9 knockout (GeCKO) library to screen for drugs that overcome treatment resistance and to identify the potential drug-resistant genes involved in treatment resistance. Our screening results showed that the DNA-damaging agent idarubicin (IDA) overcame abiraterone and enzalutamide resistance in prostate cancer cells. IDA treatment inhibited the DNA repair protein XPA expression in a transcription-independent manner. Consistently, XPA knockout sensitized prostate cancer cells to abiraterone and enzalutamide treatment. In conclusion, IDA combats abiraterone and enzalutamide resistance by reducing XPA protein level in prostate cancer.

UR - http://www.scopus.com/inward/record.url?scp=85143730916&partnerID=8YFLogxK

U2 - 10.1038/s41419-022-05490-5

DO - 10.1038/s41419-022-05490-5

M3 - Article

C2 - 36509750

AN - SCOPUS:85143730916

SN - 2041-4889

VL - 13

JO - Cell Death and Disease

JF - Cell Death and Disease

IS - 12

M1 - 1034

ER -

Idarubicin combats abiraterone and enzalutamide resistance in prostate cells via targeting XPA protein

Abstract

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