Cargando…

Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action

BACKGROUND: Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical...

Descripción completa

Detalles Bibliográficos
Autores principales: Wadhwa, Renu, Singh, Rumani, Gao, Ran, Shah, Navjot, Widodo, Nashi, Nakamoto, Tomoko, Ishida, Yoshiyuki, Terao, Keiji, Kaul, Sunil C.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2013
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795014/
https://www.ncbi.nlm.nih.gov/pubmed/24130852
http://dx.doi.org/10.1371/journal.pone.0077189
_version_ 1782287316736278528
author Wadhwa, Renu
Singh, Rumani
Gao, Ran
Shah, Navjot
Widodo, Nashi
Nakamoto, Tomoko
Ishida, Yoshiyuki
Terao, Keiji
Kaul, Sunil C.
author_facet Wadhwa, Renu
Singh, Rumani
Gao, Ran
Shah, Navjot
Widodo, Nashi
Nakamoto, Tomoko
Ishida, Yoshiyuki
Terao, Keiji
Kaul, Sunil C.
author_sort Wadhwa, Renu
collection PubMed
description BACKGROUND: Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX). METHODOLOGY/PRINCIPAL FINDINGS: Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected. CONCLUSION: We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine.
format Online
Article
Text
id pubmed-3795014
institution National Center for Biotechnology Information
language English
publishDate 2013
publisher Public Library of Science
record_format MEDLINE/PubMed
spelling pubmed-37950142013-10-15 Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action Wadhwa, Renu Singh, Rumani Gao, Ran Shah, Navjot Widodo, Nashi Nakamoto, Tomoko Ishida, Yoshiyuki Terao, Keiji Kaul, Sunil C. PLoS One Research Article BACKGROUND: Cancer is a leading cause of death accounting for 15-20% of global mortality. Although advancements in diagnostic and therapeutic technologies have improved cancer survival statistics, 75% of the world population live in underdeveloped regions and have poor access to the advanced medical remedies. Natural therapies hence become an alternative choice of treatment. Ashwagandha, a tropical herb used in Indian Ayurvedic medicine, has a long history of its health promoting and therapeutic effects. In the present study, we have investigated an anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX). METHODOLOGY/PRINCIPAL FINDINGS: Anticancer activity in the water extract of Ashwagandha leaves (ASH-WEX) was detected by in vitro and in vivo assays. Bioactivity-based size fractionation and NMR analysis were performed to identify the active anticancer component(s). Mechanism of anticancer activity in the extract and its purified component was investigated by biochemical assays. We report that the ASH-WEX is cytotoxic to cancer cells selectively, and causes tumor suppression in vivo. Its active anticancer component was identified as triethylene glycol (TEG). Molecular analysis revealed activation of tumor suppressor proteins p53 and pRB by ASH-WEX and TEG in cancer cells. In contrast to the hypophosphorylation of pRB, decrease in cyclin B1 and increase in cyclin D1 in ASH-WEX and TEG-treated cancer cells (undergoing growth arrest), normal cells showed increase in pRB phosphorylation and cyclin B1, and decrease in cyclin D1 (signifying their cell cycle progression). We also found that the MMP-3 and MMP-9 that regulate metastasis were down regulated in ASH-WEX and TEG-treated cancer cells; normal cells remained unaffected. CONCLUSION: We provide the first molecular evidence that the ASH-WEX and TEG have selective cancer cell growth arrest activity and hence may offer natural and economic resources for anticancer medicine. Public Library of Science 2013-10-10 /pmc/articles/PMC3795014/ /pubmed/24130852 http://dx.doi.org/10.1371/journal.pone.0077189 Text en © 2013 Wadhwa et al http://creativecommons.org/licenses/by/4.0/ 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 properly credited.
spellingShingle Research Article
Wadhwa, Renu
Singh, Rumani
Gao, Ran
Shah, Navjot
Widodo, Nashi
Nakamoto, Tomoko
Ishida, Yoshiyuki
Terao, Keiji
Kaul, Sunil C.
Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title_full Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title_fullStr Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title_full_unstemmed Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title_short Water Extract of Ashwagandha Leaves Has Anticancer Activity: Identification of an Active Component and Its Mechanism of Action
title_sort water extract of ashwagandha leaves has anticancer activity: identification of an active component and its mechanism of action
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3795014/
https://www.ncbi.nlm.nih.gov/pubmed/24130852
http://dx.doi.org/10.1371/journal.pone.0077189
work_keys_str_mv AT wadhwarenu waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT singhrumani waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT gaoran waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT shahnavjot waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT widodonashi waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT nakamototomoko waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT ishidayoshiyuki waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT teraokeiji waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction
AT kaulsunilc waterextractofashwagandhaleaveshasanticanceractivityidentificationofanactivecomponentanditsmechanismofaction