Lack of metformin effects on different molecular subtypes of breast cancer under normoglycemic conditions: an in vitro study.
BACKGROUND
In the past few years, a considerable number of preclinical studies have been proposed metformin as a potential anticancer agent, but some of these studies suffer from a number of methodological limitations such as assessment of cytotoxicity in the presence of supraphysiological glucose concentrations or applying suprapharmacological levels of the drug. These objections have limited the translation of published preclinical data to the clinical setting. The present study aimed to investigate direct anticancer effects of metformin on different molecular subtypes of breast cancer with pharmacological concentrations and under normoglycemic conditions in vitro.


METHODS
Breast cancer cell lines from luminal A, luminal B, ErbB2 and triple-negative molecular subtypes were treated with a pharmacological concentration of metformin (2mM) at a glucose concentration of 5.5mM. Time-dependant cell viability was assessed by dye exclusion assay. MTT- based cytotoxicity assays were also performed with metformin alone or in combination with paclitaxel.


RESULTS
Metformin did not show any growth inhibitory effects or time-dependant cytotoxicity on breast cancer cell lines in the presence of normal glucose concentrations at the therapeutic plasma level. No augmentation of the anti- neoplastic properties of paclitaxel was apparent under the tested conditions.


CONCLUSIONS
Metformin is probably unable to exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels. These results highlight the importance of establishing a higher steady-state plasma concentration of metformin in the clinical setting for assessment of anticancer effects in normoglycemic patients.
Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran E-mail : smuhammadnejad@gmail.com.
Sanambar
S
Sadighi
Saeid
S
Amanpour
Bita
B
Behrouzi
Zhinoos
Z
Khorgami
Samad
S
Muhammadnejad
D000970:Antineoplastic Agents / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D005260:Female; D006801:Humans; D061986:MCF-7 Cells; D008687:Metformin / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology
D000970:Antineoplastic Agents; D008687:Metformin; D017239:Paclitaxel