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...
Autores principales: | , , , , , |
---|---|
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 |