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
2020
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ftdoajarticles:oai:doaj.org/article:857c2167a93e46aa8f1c9675bf583ed1 2023-05-15T15:10:24+02:00 Achillea biebersteinii extracts suppress angiogenesis and enhance sensitivity to 5-fluorouracil of human colon cancer cells via the PTEN/AKT/mTOR pathway in vitro Mehmet Kadir Erdogan Can Ali Ağca Hakan Aşkın 2020-01-01T00:00:00Z https://doi.org/10.4103/2221-1691.294091 https://doaj.org/article/857c2167a93e46aa8f1c9675bf583ed1 EN eng Wolters Kluwer Medknow Publications http://www.apjtb.org/article.asp?issn=2221-1691;year=2020;volume=10;issue=11;spage=505;epage=515;aulast=Erdogan https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.294091 https://doaj.org/article/857c2167a93e46aa8f1c9675bf583ed1 Asian Pacific Journal of Tropical Biomedicine, Vol 10, Iss 11, Pp 505-515 (2020) achillea biebersteinii colorectal cancer chemosensitization apoptosis angiogenesis mtor Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 article 2020 ftdoajarticles https://doi.org/10.4103/2221-1691.294091 2022-12-31T15:52:30Z 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. Article in Journal/Newspaper Arctic Directory of Open Access Journals: DOAJ Articles Arctic Asian Pacific Journal of Tropical Biomedicine 10 11 505 |
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Open Polar |
collection |
Directory of Open Access Journals: DOAJ Articles |
op_collection_id |
ftdoajarticles |
language |
English |
topic |
achillea biebersteinii colorectal cancer chemosensitization apoptosis angiogenesis mtor Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
spellingShingle |
achillea biebersteinii colorectal cancer chemosensitization apoptosis angiogenesis mtor Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 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 |
topic_facet |
achillea biebersteinii colorectal cancer chemosensitization apoptosis angiogenesis mtor Arctic medicine. Tropical medicine RC955-962 Biology (General) QH301-705.5 |
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. |
format |
Article in Journal/Newspaper |
author |
Mehmet Kadir Erdogan Can Ali Ağca Hakan Aşkın |
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 |
publishDate |
2020 |
url |
https://doi.org/10.4103/2221-1691.294091 https://doaj.org/article/857c2167a93e46aa8f1c9675bf583ed1 |
geographic |
Arctic |
geographic_facet |
Arctic |
genre |
Arctic |
genre_facet |
Arctic |
op_source |
Asian Pacific Journal of Tropical Biomedicine, Vol 10, Iss 11, Pp 505-515 (2020) |
op_relation |
http://www.apjtb.org/article.asp?issn=2221-1691;year=2020;volume=10;issue=11;spage=505;epage=515;aulast=Erdogan https://doaj.org/toc/2221-1691 https://doaj.org/toc/2588-9222 2221-1691 2588-9222 doi:10.4103/2221-1691.294091 https://doaj.org/article/857c2167a93e46aa8f1c9675bf583ed1 |
op_doi |
https://doi.org/10.4103/2221-1691.294091 |
container_title |
Asian Pacific Journal of Tropical Biomedicine |
container_volume |
10 |
container_issue |
11 |
container_start_page |
505 |
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1766341436746235904 |