Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells
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2015
Authors
Damjanović, Ana B.
Matić, Ivana Z.

Dordić, Marija
Nikolić-Durović, Marina
Nikolić, Srdan
Roki, Ksenija
Milovanović, Zorka
Antić-Stanković, Jelena

Dzodić, Radan

Damjanović, Svetozar S.
Kanjer, Ksenija
Abu Rabi, Zaki
Juranić, Zorica
Article (Published version)

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The aim of research was to determine the effects of maximally therapeutically achievable concentrations of metformin on malignant cells and healthy peripheral blood mononuclear cells (PBMC). Eight patients with T2D or hyperglycemia and nine healthy volunteers were included in the study. For determination of the influence of metformin on the phenotype of breast carcinoma, 1,410 patients with surgically removed tumors were included. From this group 37 breast cancer patients had DM type 2 or hyperglycemia and were pretreated with metformin alone or sometimes in combination with other antidiabetic drugs. Our results proved that metformin at low concentrations induced mild decrease in survival of malignant cells and PBMC stimulated for proliferation, but it didn't affect survival of resting PBMC. The effects of plasma of hyperglycemic patients who were under metformin therapy on autologous PBMC-induced decrease in survival of MDA-MB-361 cells, was noticeable in some patients. Metformin pret...reatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival. The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p lt 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p lt 0.832). In conclusion, therapeutically used concentrations of metformin exhibit mild cytotoxic action on malignant and dividing normal cells pointing to its preferred role in malignant and autoimmune diseases. The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors.
Keywords:
Cancer / Herceptin / Metformin / PBMCSource:
Pathology & Oncology Research, 2015, 21, 3, 605-612Publisher:
- Springer, Dordrecht
Funding / projects:
DOI: 10.1007/s12253-014-9864-9
ISSN: 1219-4956
PubMed: 25351941
WoS: 000355624700012
Scopus: 2-s2.0-84938074955
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PharmacyTY - JOUR AU - Damjanović, Ana B. AU - Matić, Ivana Z. AU - Dordić, Marija AU - Nikolić-Durović, Marina AU - Nikolić, Srdan AU - Roki, Ksenija AU - Milovanović, Zorka AU - Antić-Stanković, Jelena AU - Dzodić, Radan AU - Damjanović, Svetozar S. AU - Kanjer, Ksenija AU - Abu Rabi, Zaki AU - Juranić, Zorica PY - 2015 UR - https://farfar.pharmacy.bg.ac.rs/handle/123456789/2457 AB - The aim of research was to determine the effects of maximally therapeutically achievable concentrations of metformin on malignant cells and healthy peripheral blood mononuclear cells (PBMC). Eight patients with T2D or hyperglycemia and nine healthy volunteers were included in the study. For determination of the influence of metformin on the phenotype of breast carcinoma, 1,410 patients with surgically removed tumors were included. From this group 37 breast cancer patients had DM type 2 or hyperglycemia and were pretreated with metformin alone or sometimes in combination with other antidiabetic drugs. Our results proved that metformin at low concentrations induced mild decrease in survival of malignant cells and PBMC stimulated for proliferation, but it didn't affect survival of resting PBMC. The effects of plasma of hyperglycemic patients who were under metformin therapy on autologous PBMC-induced decrease in survival of MDA-MB-361 cells, was noticeable in some patients. Metformin pretreatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival. The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p lt 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p lt 0.832). In conclusion, therapeutically used concentrations of metformin exhibit mild cytotoxic action on malignant and dividing normal cells pointing to its preferred role in malignant and autoimmune diseases. The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors. PB - Springer, Dordrecht T2 - Pathology & Oncology Research T1 - Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells VL - 21 IS - 3 SP - 605 EP - 612 DO - 10.1007/s12253-014-9864-9 ER -
@article{ author = "Damjanović, Ana B. and Matić, Ivana Z. and Dordić, Marija and Nikolić-Durović, Marina and Nikolić, Srdan and Roki, Ksenija and Milovanović, Zorka and Antić-Stanković, Jelena and Dzodić, Radan and Damjanović, Svetozar S. and Kanjer, Ksenija and Abu Rabi, Zaki and Juranić, Zorica", year = "2015", abstract = "The aim of research was to determine the effects of maximally therapeutically achievable concentrations of metformin on malignant cells and healthy peripheral blood mononuclear cells (PBMC). Eight patients with T2D or hyperglycemia and nine healthy volunteers were included in the study. For determination of the influence of metformin on the phenotype of breast carcinoma, 1,410 patients with surgically removed tumors were included. From this group 37 breast cancer patients had DM type 2 or hyperglycemia and were pretreated with metformin alone or sometimes in combination with other antidiabetic drugs. Our results proved that metformin at low concentrations induced mild decrease in survival of malignant cells and PBMC stimulated for proliferation, but it didn't affect survival of resting PBMC. The effects of plasma of hyperglycemic patients who were under metformin therapy on autologous PBMC-induced decrease in survival of MDA-MB-361 cells, was noticeable in some patients. Metformin pretreatment for 24 h of HER2+ MDA-MB-361 cells, which were subsequently treated for 48 h with Herceptin, induced additional decline in cell survival. The analysis of influence of metformin on phenotype of breast cancer cells revealed significantly lower number of diabetic cancer patients treated with metformin with overexpressed HER2+ tumors (p lt 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p lt 0.832). In conclusion, therapeutically used concentrations of metformin exhibit mild cytotoxic action on malignant and dividing normal cells pointing to its preferred role in malignant and autoimmune diseases. The use of metformin was associated with pronounced decrease in HER2 overexpressing tumors.", publisher = "Springer, Dordrecht", journal = "Pathology & Oncology Research", title = "Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells", volume = "21", number = "3", pages = "605-612", doi = "10.1007/s12253-014-9864-9" }
Damjanović, A. B., Matić, I. Z., Dordić, M., Nikolić-Durović, M., Nikolić, S., Roki, K., Milovanović, Z., Antić-Stanković, J., Dzodić, R., Damjanović, S. S., Kanjer, K., Abu Rabi, Z.,& Juranić, Z.. (2015). Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells. in Pathology & Oncology Research Springer, Dordrecht., 21(3), 605-612. https://doi.org/10.1007/s12253-014-9864-9
Damjanović AB, Matić IZ, Dordić M, Nikolić-Durović M, Nikolić S, Roki K, Milovanović Z, Antić-Stanković J, Dzodić R, Damjanović SS, Kanjer K, Abu Rabi Z, Juranić Z. Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells. in Pathology & Oncology Research. 2015;21(3):605-612. doi:10.1007/s12253-014-9864-9 .
Damjanović, Ana B., Matić, Ivana Z., Dordić, Marija, Nikolić-Durović, Marina, Nikolić, Srdan, Roki, Ksenija, Milovanović, Zorka, Antić-Stanković, Jelena, Dzodić, Radan, Damjanović, Svetozar S., Kanjer, Ksenija, Abu Rabi, Zaki, Juranić, Zorica, "Metformin Effects on Malignant Cells and Healthy PBMC; The Influence of Metformin on the Phenotype of Breast Cancer Cells" in Pathology & Oncology Research, 21, no. 3 (2015):605-612, https://doi.org/10.1007/s12253-014-9864-9 . .