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Efficacy of metformin and electrical pulses in breast cancer MDA-MB-231 cells
Praveen Sahu1, Ignacio G Camarillo2,3, Raji Sundararajan1
1School of Engineering Technology, Purdue University, West Lafayette, IN 47907, USA.
Aim:
Triple-negative breast cancer (TNBC) is a very aggressive subset of breast cancer, with limited treatment options, due to the lack of three commonly targeted receptors, which merits the need for novel treatments for TNBC. Towards this need, the use of metformin (Met), the most widely used type-2 diabetes drug worldwide, was explored as a repurposed anticancer agent. Cancer being a metabolic disease, the modulation of two crucial metabolites, glucose, and reactive oxygen species (ROS), is studied in MDA-MB-231 TNBC cells, using Met in the presence of electrical pulses (EP) to enhance the drug efficacy.
Methods:
MDA-MB-231, human TNBC cells were treated with Met in the presence of EP, with various concentrations Met of 1 mmol/L, 2.5 mmol/L, 5 mmol/L, and 10 mmol/L. EP of 500 V/cm, 800 V/cm, and 1,000 V/cm (with a pulse width of 100 µs at 1 s intervals) were applied to TNBC and the impact of these two treatments was studied. Various assays, including cell viability, microscopic inspection, glucose, ROS, and wound healing assay, were performed to characterize the response of the cells to the combination treatment.
Results:
Combining 1,000 V/cm with 5 mmol/L Met yielded cell viability as low as 42.6% at 24 h. The glucose level was reduced by 5.60-fold and the ROS levels were increased by 9.56-fold compared to the control, leading to apoptotic cell death.
Conclusions:
The results indicate the enhanced anticancer effect of Met in the presence of electric pulses. The cell growth is inhibited by suppressing glucose levels and elevated ROS. This shows a synergistic interplay between electroporation, Met, glucose, and ROS metabolic alterations. The results show promises for combinational therapy in TNBC patients.
Insights
Metformin combined with electrical pulses shows promise for treating triple-negative breast cancer (TNBC) by reducing glucose and increasing reactive oxygen species (ROS), leading to cancer cell death.
Area of Science:
- Oncology
- Biochemistry
- Biophysics
Background:
- Triple-negative breast cancer (TNBC) is an aggressive cancer subtype with limited therapeutic options.
- Metformin, a type-2 diabetes drug, is being investigated as a repurposed anticancer agent.
- Cancer's metabolic nature necessitates exploring metabolite modulation for novel treatments.
Purpose of the Study:
- To investigate the efficacy of metformin (Met) as a repurposed anticancer agent for TNBC.
- To explore the combined effect of metformin and electrical pulses (EP) on TNBC cells.
- To analyze the impact of Met and EP on glucose and reactive oxygen species (ROS) levels in TNBC cells.
Main Methods:
- MDA-MB-231 human TNBC cells were treated with varying concentrations of Met (1-10 mmol/L) and EP (500-1,000 V/cm).
- Cell viability, glucose uptake, ROS production, and wound healing were assessed.
- The synergistic effects of Met and EP on metabolic alterations were characterized.
Main Results:
- Combining 5 mmol/L Met with 1,000 V/cm EP reduced cell viability to 42.6% within 24 hours.
- Glucose levels decreased 5.60-fold, and ROS levels increased 9.56-fold compared to controls.
- The combination treatment induced apoptotic cell death.
Conclusions:
- Metformin enhances anticancer effects when combined with electrical pulses in TNBC.
- The combination therapy inhibits cell growth by suppressing glucose and elevating ROS.
- This synergistic interplay suggests a promising therapeutic strategy for TNBC patients.
