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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Wolters Kluwer Medknow Publications
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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 |
work_keys_str_mv |
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