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Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

Liu Z, Ren L, Liu C, Xia T, Zha X, Wang S - PLoS ONE (2015)

Bottom Line: Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin.Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice.Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error). Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition) and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

No MeSH data available.


Related in: MedlinePlus

Phenformin induces cell death of breast cancer cell.Cells were grown for 24 hours in the presence of the indicated concentration of phenformin. CCK-8 assays were performed to evaluate cell viability. The absorbance was measured at 450 nm using an automated microplate reader. The percent growth inhibition was calculated using the following formula: (OD of the control-OD of the experimental sample)/OD of the control×100%.
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pone.0131207.g001: Phenformin induces cell death of breast cancer cell.Cells were grown for 24 hours in the presence of the indicated concentration of phenformin. CCK-8 assays were performed to evaluate cell viability. The absorbance was measured at 450 nm using an automated microplate reader. The percent growth inhibition was calculated using the following formula: (OD of the control-OD of the experimental sample)/OD of the control×100%.

Mentions: To evaluate the activity of phenformin in breast cancer cell lines of different genetic backgrounds, two ERα-positive breast cancer cell lines (MCF7, ZR-75-1) and two ERα-negative breast cancer cell lines (MDA-MB-231, SUM1315) were used. The CCK-8 assay was used to detect the inhibitory effect of phenformin on the different breast cancer cell lines. Increasing doses of phenformin resulted in a dose-dependent cell death of all 4 breast cancer cell lines. MCF7 and ZR-75-1 cells were more sensitive to phenformin, whereas MDA-MB-231 and SUM1315 cells were less sensitive to phenformin (Fig 1). The respective IC50 values of phenformin in the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error).


Phenformin Induces Cell Cycle Change, Apoptosis, and Mesenchymal-Epithelial Transition and Regulates the AMPK/mTOR/p70s6k and MAPK/ERK Pathways in Breast Cancer Cells.

Liu Z, Ren L, Liu C, Xia T, Zha X, Wang S - PLoS ONE (2015)

Phenformin induces cell death of breast cancer cell.Cells were grown for 24 hours in the presence of the indicated concentration of phenformin. CCK-8 assays were performed to evaluate cell viability. The absorbance was measured at 450 nm using an automated microplate reader. The percent growth inhibition was calculated using the following formula: (OD of the control-OD of the experimental sample)/OD of the control×100%.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4482683&req=5

pone.0131207.g001: Phenformin induces cell death of breast cancer cell.Cells were grown for 24 hours in the presence of the indicated concentration of phenformin. CCK-8 assays were performed to evaluate cell viability. The absorbance was measured at 450 nm using an automated microplate reader. The percent growth inhibition was calculated using the following formula: (OD of the control-OD of the experimental sample)/OD of the control×100%.
Mentions: To evaluate the activity of phenformin in breast cancer cell lines of different genetic backgrounds, two ERα-positive breast cancer cell lines (MCF7, ZR-75-1) and two ERα-negative breast cancer cell lines (MDA-MB-231, SUM1315) were used. The CCK-8 assay was used to detect the inhibitory effect of phenformin on the different breast cancer cell lines. Increasing doses of phenformin resulted in a dose-dependent cell death of all 4 breast cancer cell lines. MCF7 and ZR-75-1 cells were more sensitive to phenformin, whereas MDA-MB-231 and SUM1315 cells were less sensitive to phenformin (Fig 1). The respective IC50 values of phenformin in the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error).

Bottom Line: Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin.Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice.Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

View Article: PubMed Central - PubMed

Affiliation: Department of Breast Surgery, the First Affiliated Hospital of Nanjing Medical University, Nanjing, China.

ABSTRACT
Breast cancer remains a world-wide challenge, and additional anti-cancer therapies are still urgently needed. Emerging evidence has demonstrated the potent anti-tumor effect of biguanides, among which phenformin was reported to potentially be a more active anti-cancer agent than metformin. However, little attention has been given to the role of phenformin in breast cancer. In this study, we reveal the role of phenformin in cell death of the MCF7, ZR-75-1, MDA-MB-231 and SUM1315 breast cancer cell lines. The respective IC50 values of phenformin in MCF7, ZR-75-1, MDA-MB-231 and SUM1315 cells were 1.184±0.045 mM, 0.665±0.007 mM, 2.347±0.010 mM and 1.885±0.015 mM (mean± standard error). Phenformin induced cell cycle change and apoptosis in breast cancer cells via the AMPK/mTOR/p70s6k and MAPK/ERK pathways. Interestingly, phenformin induced MET (mesenchymal-epithelial transition) and decreased the migration rate in breast cancer cell lines. Furthermore, our results suggest that phenformin inhibits breast cancer cell metastasis after intracardiac injection into nude mice. Taken together, our study further confirms the potential benefit of phenformin in breast cancer treatment and provides novel mechanistic insight into its anti-cancer activity in breast cancer.

No MeSH data available.


Related in: MedlinePlus