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ORIGINAL ARTICLE
Year : 2020  |  Volume : 10  |  Issue : 11  |  Page : 505-515

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


1 Department of Biology, Faculty of Arts and Sciences, Bingol University, 12000, Bingol, Turkey
2 Department of Molecular Biology and Genetics, Faculty of Arts and Sciences, Bingol University, 12000, Bingol, Turkey
3 Department of Molecular Biology and Genetics, Faculty of Sciences, Ataturk University, 25000, Erzurum, Turkey

Correspondence Address:
Mehmet Kadir Erdogan
Department of Biology, Faculty of Arts and Sciences, Bingol University, 12000, Bingol
Turkey
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Source of Support: This work was supported by The Scientific Research Projects Coordination Unit of Ataturk University (Project no: AUBAP2013- 292) and The Scientific Research Projects Coordination Unit of Bingol University (Project no: BAP-FEF.2017.00.010), Conflict of Interest: None


DOI: 10.4103/2221-1691.294091

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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.


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