title: Metformin effects on malignant cells and healthy PBMC; the influence of metformin on the phenotype of breast cancer cells.
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 < 0.013), while the number of patients with ER+PR+ tumors was not significantly changed (p < 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.
authors.affiliation: Institute of Oncology and Radiology of Serbia, Pasterova 14, 11000, Belgrade, Serbia.
authors.forename: Ana
authors.initials: A
authors.lastname: Damjanović
authors.forename: Ivana Z
authors.initials: IZ
authors.lastname: Matić
authors.forename: Marija
authors.initials: M
authors.lastname: Ðorđić
authors.forename: Marina Nikolić
authors.initials: MN
authors.lastname: Ðurović
authors.forename: Srđan
authors.initials: S
authors.lastname: Nikolić
authors.forename: Ksenija
authors.initials: K
authors.lastname: Roki
authors.forename: Zorka
authors.initials: Z
authors.lastname: Milovanović
authors.forename: Jelena
authors.initials: J
authors.lastname: Antić-Stanković
authors.forename: Radan
authors.initials: R
authors.lastname: Džodić
authors.forename: Svetozar
authors.initials: S
authors.lastname: Damjanović
authors.forename: Ksenija
authors.initials: K
authors.lastname: Kanjer
authors.forename: Zaki
authors.initials: Z
authors.lastname: Abu Rabi
authors.forename: Zorica
authors.initials: Z
authors.lastname: Juranić
mesh_terms: D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology*; D049109:Cell Proliferation / Q000187:drug effects; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy / Q000503:physiopathology*; D005260:Female; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D008687:Metformin / Q000494:pharmacology*; D010641:Phenotype; D018719:Erb-b2 Receptor Tyrosine Kinases / Q000378:metabolism*; D000068878:Trastuzumab / Q000627:therapeutic use; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D007004:Hypoglycemic Agents; D008687:Metformin; D018719:Erb-b2 Receptor Tyrosine Kinases; D000068878:Trastuzumab