Cargando…
The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells
Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts for identification of safer and more effective metformin mimetic compounds. The plant Ficus microcarpa is widely used...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Impact Journals LLC
2015
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826172/ https://www.ncbi.nlm.nih.gov/pubmed/26683363 http://dx.doi.org/10.18632/oncotarget.6625 |
_version_ | 1782426296982175744 |
---|---|
author | Akhtar, Nosheen Syed, Deeba N. Khan, Mohammad Imran Adhami, Vaqar M. Mirza, Bushra Mukhtar, Hasan |
author_facet | Akhtar, Nosheen Syed, Deeba N. Khan, Mohammad Imran Adhami, Vaqar M. Mirza, Bushra Mukhtar, Hasan |
author_sort | Akhtar, Nosheen |
collection | PubMed |
description | Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts for identification of safer and more effective metformin mimetic compounds. The plant Ficus microcarpa is widely used for the treatment of type 2 diabetes in traditional medicine in South Asia. We obtained extracts from this plant and identified a small molecule, plectranthoic acid (PA), with potent 5′AMP-activated kinase (AMPK) activating properties far superior than metformin. AMPK is the central hub of metabolic regulation and a well-studied therapeutic target for metabolic syndrome, type-2 diabetes and cancer. We observed that treatment of prostate cancer (PCa) cells with PA inhibited proliferation and induced G0/G1 phase cell cycle arrest that was associated with up-regulation of cyclin kinase inhibitors p21/CIP1 and p27/KIP1. PA treatment suppressed mTOR/S6K signaling and induced apoptosis in PCa cells in an AMPK-dependent manner. Interestingly, PA-induced autophagy in PCa cells was found to be independent of AMPK activation. Combination studies of PA and metformin demonstrated that metformin had an inhibitory effect on PA-induced AMPK activation and suppressed PA-mediated apoptosis. Given the anti-proliferative role of PA in cancer and its potent anti-hyperglycemic activity, we suggest that PA should be explored further as a novel activator of AMPK for its ultimate use for the prevention of cancers and treatment of type 2 diabetes. |
format | Online Article Text |
id | pubmed-4826172 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2015 |
publisher | Impact Journals LLC |
record_format | MEDLINE/PubMed |
spelling | pubmed-48261722016-05-09 The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells Akhtar, Nosheen Syed, Deeba N. Khan, Mohammad Imran Adhami, Vaqar M. Mirza, Bushra Mukhtar, Hasan Oncotarget Research Paper Epidemiologic studies indicated that diabetics treated with metformin had a lower incidence of cancer than those taking other anti-diabetes drugs. This led to a surge in the efforts for identification of safer and more effective metformin mimetic compounds. The plant Ficus microcarpa is widely used for the treatment of type 2 diabetes in traditional medicine in South Asia. We obtained extracts from this plant and identified a small molecule, plectranthoic acid (PA), with potent 5′AMP-activated kinase (AMPK) activating properties far superior than metformin. AMPK is the central hub of metabolic regulation and a well-studied therapeutic target for metabolic syndrome, type-2 diabetes and cancer. We observed that treatment of prostate cancer (PCa) cells with PA inhibited proliferation and induced G0/G1 phase cell cycle arrest that was associated with up-regulation of cyclin kinase inhibitors p21/CIP1 and p27/KIP1. PA treatment suppressed mTOR/S6K signaling and induced apoptosis in PCa cells in an AMPK-dependent manner. Interestingly, PA-induced autophagy in PCa cells was found to be independent of AMPK activation. Combination studies of PA and metformin demonstrated that metformin had an inhibitory effect on PA-induced AMPK activation and suppressed PA-mediated apoptosis. Given the anti-proliferative role of PA in cancer and its potent anti-hyperglycemic activity, we suggest that PA should be explored further as a novel activator of AMPK for its ultimate use for the prevention of cancers and treatment of type 2 diabetes. Impact Journals LLC 2015-12-16 /pmc/articles/PMC4826172/ /pubmed/26683363 http://dx.doi.org/10.18632/oncotarget.6625 Text en Copyright: © 2016 Akhtar et al. http://creativecommons.org/licenses/by/2.5/ This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. |
spellingShingle | Research Paper Akhtar, Nosheen Syed, Deeba N. Khan, Mohammad Imran Adhami, Vaqar M. Mirza, Bushra Mukhtar, Hasan The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title | The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title_full | The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title_fullStr | The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title_full_unstemmed | The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title_short | The pentacyclic triterpenoid, plectranthoic acid, a novel activator of AMPK induces apoptotic death in prostate cancer cells |
title_sort | pentacyclic triterpenoid, plectranthoic acid, a novel activator of ampk induces apoptotic death in prostate cancer cells |
topic | Research Paper |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4826172/ https://www.ncbi.nlm.nih.gov/pubmed/26683363 http://dx.doi.org/10.18632/oncotarget.6625 |
work_keys_str_mv | AT akhtarnosheen thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT syeddeeban thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT khanmohammadimran thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT adhamivaqarm thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT mirzabushra thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT mukhtarhasan thepentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT akhtarnosheen pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT syeddeeban pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT khanmohammadimran pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT adhamivaqarm pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT mirzabushra pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells AT mukhtarhasan pentacyclictriterpenoidplectranthoicacidanovelactivatorofampkinducesapoptoticdeathinprostatecancercells |