Cargando…

Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective

Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin ag...

Descripción completa

Detalles Bibliográficos
Autores principales: Mosli, Hala H., Esmat, Ahmed, Atawia, Reem T., Shoieb, Sherif M., Mosli, Hisham A., Abdel-Naim, Ashraf B.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group 2015
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616049/
https://www.ncbi.nlm.nih.gov/pubmed/26492952
http://dx.doi.org/10.1038/srep15639
_version_ 1782396555552096256
author Mosli, Hala H.
Esmat, Ahmed
Atawia, Reem T.
Shoieb, Sherif M.
Mosli, Hisham A.
Abdel-Naim, Ashraf B.
author_facet Mosli, Hala H.
Esmat, Ahmed
Atawia, Reem T.
Shoieb, Sherif M.
Mosli, Hisham A.
Abdel-Naim, Ashraf B.
author_sort Mosli, Hala H.
collection PubMed
description Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation.
format Online
Article
Text
id pubmed-4616049
institution National Center for Biotechnology Information
language English
publishDate 2015
publisher Nature Publishing Group
record_format MEDLINE/PubMed
spelling pubmed-46160492015-10-29 Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective Mosli, Hala H. Esmat, Ahmed Atawia, Reem T. Shoieb, Sherif M. Mosli, Hisham A. Abdel-Naim, Ashraf B. Sci Rep Article Benign prostatic hyperplasia (BPH) is uncontrolled proliferation of prostate tissue. Metformin, a widely prescribed anti-diabetic agent, possesses anticancer activity through induction of apoptotic signaling and cell cycle arrest. This study aimed to investigate the protective effect of metformin against experimentally-induced BPH in rats. Treatment with 500 and 1000 mg/kg metformin orally for 14 days significantly inhibited testosterone-mediated increase in the prostate weight & prostate index (prostate weight/body weight [mg/g]) and attenuated the pathological alterations induced by testosterone. Mechanistically, metformin significantly protected against testosterone-induced elevation of estrogen receptor-α (ER-α) and decrease of estrogen receptor-β (ER-β) expression, with no significant effect of androgen receptor (AR) and 5α-reductase expression. It decreased mRNA expression of IGF-1 and IGF-1R and protein expression ratio of pAkt/total Akt induced by testosterone. Furthermore, it significantly ameliorated testosterone–induced reduction of mRNA expression Bax/Bcl-2 ratio, P21 and phosphatase and tensin homolog (PTEN) and AMPK [PT-172] activity. In conclusion, these findings elucidate the effectiveness of metformin in preventing testosterone-induced BPH in rats. These results could be attributed, at least partly, to its ability to enhance expression ratio of ER-β/ER-α, decrease IGF-1, IGF-1R and pAkt expressions, increase P21, PTEN, Bax/Bcl-2 expressions and activate AMPK with a subsequent inhibition of prostate proliferation. Nature Publishing Group 2015-10-23 /pmc/articles/PMC4616049/ /pubmed/26492952 http://dx.doi.org/10.1038/srep15639 Text en Copyright © 2015, Macmillan Publishers Limited http://creativecommons.org/licenses/by/4.0/ This work is licensed under a Creative Commons Attribution 4.0 International License. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in the credit line; if the material is not included under the Creative Commons license, users will need to obtain permission from the license holder to reproduce the material. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/
spellingShingle Article
Mosli, Hala H.
Esmat, Ahmed
Atawia, Reem T.
Shoieb, Sherif M.
Mosli, Hisham A.
Abdel-Naim, Ashraf B.
Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title_full Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title_fullStr Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title_full_unstemmed Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title_short Metformin Attenuates Testosterone-Induced Prostatic Hyperplasia in Rats: A Pharmacological Perspective
title_sort metformin attenuates testosterone-induced prostatic hyperplasia in rats: a pharmacological perspective
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4616049/
https://www.ncbi.nlm.nih.gov/pubmed/26492952
http://dx.doi.org/10.1038/srep15639
work_keys_str_mv AT moslihalah metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective
AT esmatahmed metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective
AT atawiareemt metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective
AT shoiebsherifm metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective
AT moslihishama metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective
AT abdelnaimashrafb metforminattenuatestestosteroneinducedprostatichyperplasiainratsapharmacologicalperspective