Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines

Abstract Background The androgen receptor (AR) has been studied as an approach to cancer therapy. Aims We used human breast cancer‐derived cells with high, low, and very low expression levels of AR, in addition to prostate cancer‐derived LNCaP and DU‐145 cells as a positive and negative controls to...

Full description

Bibliographic Details
Main Authors: Mazdak Jamshidi, Fatemeh Keshavarzi, Sabrieh Amini, Ismail Laher, Ali Gheysarzadeh, Kambiz Davari
Format: Article
Language:English
Published: Wiley 2024-01-01
Series:Cancer Reports
Subjects:
Online Access:https://doi.org/10.1002/cnr2.1922
_version_ 1797344821600321536
author Mazdak Jamshidi
Fatemeh Keshavarzi
Sabrieh Amini
Ismail Laher
Ali Gheysarzadeh
Kambiz Davari
author_facet Mazdak Jamshidi
Fatemeh Keshavarzi
Sabrieh Amini
Ismail Laher
Ali Gheysarzadeh
Kambiz Davari
author_sort Mazdak Jamshidi
collection DOAJ
description Abstract Background The androgen receptor (AR) has been studied as an approach to cancer therapy. Aims We used human breast cancer‐derived cells with high, low, and very low expression levels of AR, in addition to prostate cancer‐derived LNCaP and DU‐145 cells as a positive and negative controls to examine apoptosis caused by a synthetic peptide that targets ARs. Methods and Results The peptide was produced to inhibit AR transactivation in breast cancer cell lines. We then measured cell viability, caspase‐3 activity, and the ratio of Bax/Bcl‐2. The findings indicated that the peptide (100–500 nM) in the presence of dihydrotestosterone (DHT) reduced cell growth in cells with high and low expression level of AR (p < .001), but not in cells with very low levels of AR. Treatment with 100–500 nM of peptide activated caspase‐3 and increased the ratio of Bax/Bcl‐2 in cells with high and low expression levels of AR. Also, increasing concentrations of the peptide (100–500 nM) reduced BrdU incorporation in the presence of DHT and promoted apoptosis in cells with high and low expression levels of AR (p < .001). Conclusion The findings indicate the peptide significantly increased apoptosis in cancer cells.
first_indexed 2024-03-08T11:08:28Z
format Article
id doaj.art-6ba2c6a6a1f24911937e8740d966aea3
institution Directory Open Access Journal
issn 2573-8348
language English
last_indexed 2024-03-08T11:08:28Z
publishDate 2024-01-01
publisher Wiley
record_format Article
series Cancer Reports
spelling doaj.art-6ba2c6a6a1f24911937e8740d966aea32024-01-26T14:25:02ZengWileyCancer Reports2573-83482024-01-0171n/an/a10.1002/cnr2.1922Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell linesMazdak Jamshidi0Fatemeh Keshavarzi1Sabrieh Amini2Ismail Laher3Ali Gheysarzadeh4Kambiz Davari5Department of Biology, Sanandaj Branch Islamic Azad University Sanandaj IranDepartment of Biology, Sanandaj Branch Islamic Azad University Sanandaj IranDepartment of Biology, Sanandaj Branch Islamic Azad University Sanandaj IranDepartment of Anesthesiology, Pharmacology and Therapeutics The University of British Columbia Vancouver British Columbia CanadaDepartment of Clinical Biochemistry Ilam University of Medical Sciences Ilam IranDepartment of Biology, Sanandaj Branch Islamic Azad University Sanandaj IranAbstract Background The androgen receptor (AR) has been studied as an approach to cancer therapy. Aims We used human breast cancer‐derived cells with high, low, and very low expression levels of AR, in addition to prostate cancer‐derived LNCaP and DU‐145 cells as a positive and negative controls to examine apoptosis caused by a synthetic peptide that targets ARs. Methods and Results The peptide was produced to inhibit AR transactivation in breast cancer cell lines. We then measured cell viability, caspase‐3 activity, and the ratio of Bax/Bcl‐2. The findings indicated that the peptide (100–500 nM) in the presence of dihydrotestosterone (DHT) reduced cell growth in cells with high and low expression level of AR (p < .001), but not in cells with very low levels of AR. Treatment with 100–500 nM of peptide activated caspase‐3 and increased the ratio of Bax/Bcl‐2 in cells with high and low expression levels of AR. Also, increasing concentrations of the peptide (100–500 nM) reduced BrdU incorporation in the presence of DHT and promoted apoptosis in cells with high and low expression levels of AR (p < .001). Conclusion The findings indicate the peptide significantly increased apoptosis in cancer cells.https://doi.org/10.1002/cnr2.1922androgen receptoranticancer peptideapoptosisbreast cancerdihydrotestosterone (DHT)
spellingShingle Mazdak Jamshidi
Fatemeh Keshavarzi
Sabrieh Amini
Ismail Laher
Ali Gheysarzadeh
Kambiz Davari
Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
Cancer Reports
androgen receptor
anticancer peptide
apoptosis
breast cancer
dihydrotestosterone (DHT)
title Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
title_full Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
title_fullStr Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
title_full_unstemmed Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
title_short Targeting androgen receptor (AR) with a synthetic peptide increases apoptosis in triple negative breast cancer and AR‐expressing prostate cancer cell lines
title_sort targeting androgen receptor ar with a synthetic peptide increases apoptosis in triple negative breast cancer and ar expressing prostate cancer cell lines
topic androgen receptor
anticancer peptide
apoptosis
breast cancer
dihydrotestosterone (DHT)
url https://doi.org/10.1002/cnr2.1922
work_keys_str_mv AT mazdakjamshidi targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines
AT fatemehkeshavarzi targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines
AT sabriehamini targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines
AT ismaillaher targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines
AT aligheysarzadeh targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines
AT kambizdavari targetingandrogenreceptorarwithasyntheticpeptideincreasesapoptosisintriplenegativebreastcancerandarexpressingprostatecancercelllines