The electrical pulse application enhances intra-cellular localization and potentiates cytotoxicity of curcumin in breast cancer cells

•Electrical pulse application enhances intracellular uptake of curcumin derivatives.•Bisdemethoxycurcumin uptake was the highest among all curcumanoids measured.•Electrical treatment potentiated the cytotoxicity of combined CaCl2 and curcumin.•EP + Cur + CaCl2 treatment predominantly induced apoptosis with minor necrosis. Breast cancer is the most common cancer of women, and fifth leading cause of mortality worldwide. Existing breast cancer regimens are costly and produce severe side effects. This highlights a need for the development of efficient novel therapies, which are cost effective and limit side effects. An electrical pulse (EP)-based chemo therapy, known as electrochemotherapy (ECT) using the natural compound curcumin could be an effective alternative. ECT is a non-surgical modality, which produces excellent anti-tumor efficacy at small drug concentrations due to increased uptake of drugs. In clinics, ECT is shown to be effective in treating advanced, recurrent, and metastatic breast cancers, which are refractory to multiple modalities. ECT with curcumin triggers apoptotic cell death in breast cancer cells and could be an effective alternative, due to curcumin’s low cost and reduced side-effects. However, there is a lack of studies quantifying the uptake of curcumin in response to EP application. Towards this, we determined the uptake of different curcuminoids (curcumin, desmethoxycurcumin, and bisdemethoxycurcumin) upon EP application and their impact on cell cytotoxicity. Additionally, we studied the combined effect of calcium chloride (CaCl2) and a curcuminoids (Cur) mixture, based on initial studies suggesting calcium electroporation as a potential inexpensive anti-cancer treatment. Our results indicate EP with Cur increases cellular uptake, cell shrinkage, and cytotoxicity. The EP + Cur resulted in the highest uptake of the bisdemethoxycurcumin. Further, EP also potentiated the cytotoxicity of CaCl2 and of the Cur and CaCl2 combination against breast cancer cells and caused apoptosis. Our preliminary data pave the way to further studies on Cur and CaCl2 combination treating breast cancer.