Electroporation enhances cell death in 3D scaffold-based MDA-MB-231 cells treated with metformin

Bioelectrochemistry. 2024 Oct:159:108734. doi: 10.1016/j.bioelechem.2024.108734. Epub 2024 May 16.

Abstract

Triple-negative breast cancer (TNBC), the most aggressive subtype of breast cancer lacks estrogen, progesterone, and HER2 receptors and hence, is therapeutically challenging. Towards this, we studied an alternate therapy by repurposing metformin (FDA-approved type-2 diabetic drug with anticancer properties) in a 3D-scaffold culture, with electrical pulses. 3D cell culture was used to simulate the tumor microenvironment more closely and MDA-MB-231, human TNBC cells, treated with both 5 mM metformin (Met) and 8 electrical pulses at 2500 V/cm, 10 µs (EP1) and 800 V/cm, 100 µs (EP2) at 1 Hz were studied in 3D and 2D. They were characterized using cell viability, reactive oxygen species (ROS), glucose uptake, and lactate production assays at 24 h. Cell viability, as low as 20 % was obtained with EP1 + 5 mM Met. They exhibited 1.65-fold lower cell viability than 2D with EP1 + 5 mM Met. ROS levels indicated a 2-fold increase in oxidative stress for EP1 + 5 mM Met, while the glucose uptake was limited to only 9 %. No significant change in the lactate production indicated glycolytic arrest and a non-conducive environment for MDA-MB-231 growth. Our results indicate that 3D cell culture, with a more realistic tumor environment that enhances cell death using metformin and electrical pulses could be a promising approach for TNBC therapeutic intervention studies.

Keywords: 3D scaffold; Electroporation; Glucose; Lactate; MDA-MB-231; Metformin; Reactive oxygen species; Triple-negative breast cancer.

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Cell Culture Techniques, Three Dimensional / methods
  • Cell Death* / drug effects
  • Cell Line, Tumor
  • Cell Survival* / drug effects
  • Electroporation* / methods
  • Glucose / metabolism
  • Humans
  • MDA-MB-231 Cells
  • Metformin* / pharmacology
  • Reactive Oxygen Species* / metabolism
  • Tissue Scaffolds / chemistry
  • Triple Negative Breast Neoplasms / drug therapy
  • Triple Negative Breast Neoplasms / metabolism
  • Triple Negative Breast Neoplasms / pathology

Substances

  • Metformin
  • Reactive Oxygen Species
  • Glucose
  • Antineoplastic Agents