Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro

Objective: To investigate the antiproliferative, anti-angiogenic, and apoptotic effects of extracts of Achillea biebersteinii (ABE) and combined treatments of ABE with 5-fluorouracil (5-FU) on HT-29 cells. Methods: The effects of ABE, 5-FU, and combined treatments on the viability of HT-29 cells wer...

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Main Authors: Mehmet Kadir Erdogan, Can Ali Ağca, Hakan Aşkın
Format: Article
Language:English
Published: Wolters Kluwer Medknow Publications 2020-01-01
Series:Asian Pacific Journal of Tropical Biomedicine
Subjects:
Online Access:http://www.apjtb.org/article.asp?issn=2221-1691;year=2020;volume=10;issue=11;spage=505;epage=515;aulast=Erdogan
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spelling doaj-857c2167a93e46aa8f1c9675bf583ed12020-11-25T03:50:54ZengWolters Kluwer Medknow PublicationsAsian Pacific Journal of Tropical Biomedicine2221-16912588-92222020-01-01101150551510.4103/2221-1691.294091Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitroMehmet Kadir ErdoganCan Ali AğcaHakan AşkınObjective: To investigate the antiproliferative, anti-angiogenic, and apoptotic effects of extracts of Achillea biebersteinii (ABE) and combined treatments of ABE with 5-fluorouracil (5-FU) on HT-29 cells. Methods: The effects of ABE, 5-FU, and combined treatments on the viability of HT-29 cells were determined by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Isobologram analysis was used to determine synergism between ABE and 5-FU. The apoptotic and anti-angiogenic effects were determined by cell death detection and human vascular endothelial growth factor ELISA method, respectively. Transcriptional and translational expressions of p53, Bax, Bcl-2, p38 MAPK, Akt, PTEN, and mTOR were also evaluated by real-time PCR and Western blotting analysis. Results: ABE decreased the viability of HT-29 cells in a dose-dependent manner. Combined treatment of hexane, chloroform, and methanol extracts of Achillea biebersteinii with 5-FU at IC50 doses decreased the cell viability to 26.0%, 19.1%, and 14.9%, respectively (P<0.001). Furthermore, ABE treatment alone and combination with 5-FU, induced apoptosis, significantly downregulated mTOR, Akt, Bcl-2 expression, upregulated p53, Bax, PTEN, p38 MAPK expression, and exhibited anti-angiogenetic effects. Conclusions: Our findings indicate that ABE shows synergism with 5-FU and inhibits the proliferation of HT-29 cells by inducing apoptosis and suppressing angiogenesis, which may provide biological evidence for further use of ABE in the treatment of colorectal cancer.http://www.apjtb.org/article.asp?issn=2221-1691;year=2020;volume=10;issue=11;spage=505;epage=515;aulast=Erdoganachillea biebersteinii; colorectal cancer; chemosensitization; apoptosis; angiogenesis; mtor
collection DOAJ
language English
format Article
sources DOAJ
author Mehmet Kadir Erdogan
Can Ali Ağca
Hakan Aşkın
spellingShingle Mehmet Kadir Erdogan
Can Ali Ağca
Hakan Aşkın
Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
Asian Pacific Journal of Tropical Biomedicine
achillea biebersteinii; colorectal cancer; chemosensitization; apoptosis; angiogenesis; mtor
author_facet Mehmet Kadir Erdogan
Can Ali Ağca
Hakan Aşkın
author_sort Mehmet Kadir Erdogan
title Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
title_short Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
title_full Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
title_fullStr Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
title_full_unstemmed Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro
title_sort achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the pten/akt/mtor pathway in vitro
publisher Wolters Kluwer Medknow Publications
series Asian Pacific Journal of Tropical Biomedicine
issn 2221-1691
2588-9222
publishDate 2020-01-01
description Objective: To investigate the antiproliferative, anti-angiogenic, and apoptotic effects of extracts of Achillea biebersteinii (ABE) and combined treatments of ABE with 5-fluorouracil (5-FU) on HT-29 cells. Methods: The effects of ABE, 5-FU, and combined treatments on the viability of HT-29 cells were determined by 3-(4,5- dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Isobologram analysis was used to determine synergism between ABE and 5-FU. The apoptotic and anti-angiogenic effects were determined by cell death detection and human vascular endothelial growth factor ELISA method, respectively. Transcriptional and translational expressions of p53, Bax, Bcl-2, p38 MAPK, Akt, PTEN, and mTOR were also evaluated by real-time PCR and Western blotting analysis. Results: ABE decreased the viability of HT-29 cells in a dose-dependent manner. Combined treatment of hexane, chloroform, and methanol extracts of Achillea biebersteinii with 5-FU at IC50 doses decreased the cell viability to 26.0%, 19.1%, and 14.9%, respectively (P<0.001). Furthermore, ABE treatment alone and combination with 5-FU, induced apoptosis, significantly downregulated mTOR, Akt, Bcl-2 expression, upregulated p53, Bax, PTEN, p38 MAPK expression, and exhibited anti-angiogenetic effects. Conclusions: Our findings indicate that ABE shows synergism with 5-FU and inhibits the proliferation of HT-29 cells by inducing apoptosis and suppressing angiogenesis, which may provide biological evidence for further use of ABE in the treatment of colorectal cancer.
topic achillea biebersteinii; colorectal cancer; chemosensitization; apoptosis; angiogenesis; mtor
url http://www.apjtb.org/article.asp?issn=2221-1691;year=2020;volume=10;issue=11;spage=505;epage=515;aulast=Erdogan
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AT canaliagca achilleabiebersteiniiextractssuppressangiogenesisandenhancesensitivityto5fluorouracilofhumancoloncancercellsviatheptenaktmtorpathwayinvitro
AT hakanaskın achilleabiebersteiniiextractssuppressangiogenesisandenhancesensitivityto5fluorouracilofhumancoloncancercellsviatheptenaktmtorpathwayinvitro
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