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Lack of metformin effects on different molecular subtypes of breast cancer under normoglycemic conditions: an in
Sanambar Sadighi1, Saeid Amanpour, Bita Behrouzi
1Cancer Research Center, Cancer Institute of Iran, Tehran University of Medical Sciences, Tehran, Iran
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.
Materials And 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.
Insights
Metformin did not demonstrate anticancer effects on breast cancer cell lines at normal glucose levels. Further research is needed to determine optimal metformin concentrations for potential clinical use in normoglycemic patients.
Area of Science:
- Oncology
- Pharmacology
- Metabolic Diseases
Background:
- Preclinical studies suggest metformin as an anticancer agent, but methodological limitations exist.
- Previous research often used non-physiological glucose or drug concentrations, hindering clinical translation.
- This study addresses these limitations by evaluating metformin's direct anticancer effects under normoglycemic conditions.
Purpose of the Study:
- To investigate the direct anticancer effects of metformin on diverse breast cancer molecular subtypes.
- To assess metformin's efficacy at pharmacological concentrations and normal glucose levels in vitro.
- To evaluate metformin's potential synergistic effects with paclitaxel.
Main Methods:
- Breast cancer cell lines representing luminal A, luminal B, ErbB2, and triple-negative subtypes were used.
- Cells were treated with metformin (2mM) under normoglycemic conditions (5.5mM glucose).
- Cell viability and cytotoxicity were assessed using dye exclusion and MTT assays, with and without paclitaxel.
Main Results:
- Metformin exhibited no significant growth inhibition or time-dependent cytotoxicity in breast cancer cell lines at therapeutic plasma concentrations and normal glucose levels.
- No enhancement of paclitaxel's anti-neoplastic properties was observed when combined with metformin under these conditions.
- Results indicate metformin's limited direct anticancer activity in vitro under standard physiological conditions.
Conclusions:
- Metformin likely does not exert cytotoxic or cytostatic effects on breast cancer subtypes at pharmacological concentrations and normal plasma glucose levels.
- The findings underscore the need to establish higher steady-state plasma concentrations of metformin for effective anticancer assessment in normoglycemic patients.
- Optimizing metformin dosing strategies is crucial for exploring its therapeutic potential in cancer treatment.
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