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Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies

Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of Polyalthia longifolia (MEP) with pot...

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Autores principales: Afolabi, Saheed O., Olorundare, Olufunke E., Babatunde, Abiola, Albrecht, Ralph M., Koketsu, Mamoru, Syed, Deeba N., Mukhtar, Hasan
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Hindawi 2019
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881593/
https://www.ncbi.nlm.nih.gov/pubmed/31827691
http://dx.doi.org/10.1155/2019/6726312
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author Afolabi, Saheed O.
Olorundare, Olufunke E.
Babatunde, Abiola
Albrecht, Ralph M.
Koketsu, Mamoru
Syed, Deeba N.
Mukhtar, Hasan
author_facet Afolabi, Saheed O.
Olorundare, Olufunke E.
Babatunde, Abiola
Albrecht, Ralph M.
Koketsu, Mamoru
Syed, Deeba N.
Mukhtar, Hasan
author_sort Afolabi, Saheed O.
collection PubMed
description Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of Polyalthia longifolia (MEP) with potent activity against human leukemia cells. In the present study, we evaluated the efficacy of MEP against prostate cancer (PCa) and established the molecular basis of its effect in in vitro and in vivo models. We observed that MEP treatment resulted in a significant decrease in the growth and viability of PCa cells, associated with arrest in the G1/S phase of the cell cycle. Apoptosis was confirmed as the primary mode of MEP-induced cell death through activation of the intrinsic apoptotic machinery. Proteomic and biochemical studies identified BiP as an important target of MEP with the activation of the ER stress pathway, as a potential mechanism driving MEP-induced apoptosis. The extract exhibited strong efficacy in the PCa xenograft mouse model with significant inhibition of tumor growth and reduced tumor burden. Taken together, our findings indicate that MEP-induced apoptosis in PCa cells concomitant with the activation of the ER stress pathways results in the inhibition of tumor growth, in vitro and in vivo. Our studies provide initial evidence of the efficacy of MEP against PCa and advocate for in-depth studies in other preclinical models for its possible use in clinical settings.
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spelling pubmed-68815932019-12-11 Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies Afolabi, Saheed O. Olorundare, Olufunke E. Babatunde, Abiola Albrecht, Ralph M. Koketsu, Mamoru Syed, Deeba N. Mukhtar, Hasan Oxid Med Cell Longev Research Article Plant-based therapies are being explored to prevent or treat several cancer types. The antioxidant properties of Polyalthia longifolia plant are well established. In our previous work, we demonstrated the presence of cytotoxic compounds in the methanol extract of Polyalthia longifolia (MEP) with potent activity against human leukemia cells. In the present study, we evaluated the efficacy of MEP against prostate cancer (PCa) and established the molecular basis of its effect in in vitro and in vivo models. We observed that MEP treatment resulted in a significant decrease in the growth and viability of PCa cells, associated with arrest in the G1/S phase of the cell cycle. Apoptosis was confirmed as the primary mode of MEP-induced cell death through activation of the intrinsic apoptotic machinery. Proteomic and biochemical studies identified BiP as an important target of MEP with the activation of the ER stress pathway, as a potential mechanism driving MEP-induced apoptosis. The extract exhibited strong efficacy in the PCa xenograft mouse model with significant inhibition of tumor growth and reduced tumor burden. Taken together, our findings indicate that MEP-induced apoptosis in PCa cells concomitant with the activation of the ER stress pathways results in the inhibition of tumor growth, in vitro and in vivo. Our studies provide initial evidence of the efficacy of MEP against PCa and advocate for in-depth studies in other preclinical models for its possible use in clinical settings. Hindawi 2019-11-13 /pmc/articles/PMC6881593/ /pubmed/31827691 http://dx.doi.org/10.1155/2019/6726312 Text en Copyright © 2019 Saheed O. Afolabi et al. http://creativecommons.org/licenses/by/4.0/ This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
spellingShingle Research Article
Afolabi, Saheed O.
Olorundare, Olufunke E.
Babatunde, Abiola
Albrecht, Ralph M.
Koketsu, Mamoru
Syed, Deeba N.
Mukhtar, Hasan
Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title_full Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title_fullStr Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title_full_unstemmed Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title_short Polyalthia longifolia Extract Triggers ER Stress in Prostate Cancer Cells Concomitant with Induction of Apoptosis: Insights from In Vitro and In Vivo Studies
title_sort polyalthia longifolia extract triggers er stress in prostate cancer cells concomitant with induction of apoptosis: insights from in vitro and in vivo studies
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6881593/
https://www.ncbi.nlm.nih.gov/pubmed/31827691
http://dx.doi.org/10.1155/2019/6726312
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