Cell death enhancement in vitro by electroporation mediated calcium delivery

Abstract

The different methods of tumour treatment were developed based on the tumour type, stage and level, to reduce the high mortality rate of cancer patients. In the recent years, it has been shown that the method of electroporation (EP) can be successfully applied to cause cancer cell death leading to tumour loss. EP occur when the cell membrane is affected with electric field, thus causing a temporal increase of transmembrane potential leading to the formation of temporal pores in the affected cell membrane. As a result, the permeability of the affected cell membrane to hydrophilic small molecules (such as anticancer drugs) is increased [1]. The enhanced effect of transfer of anticancer drugs by using electroporation has been widely implemented for cancer treatment both in vitro and in vivo. Therefore, the electrotransfer of anticancer drug to cells can be applied in the clinics. Electrochemotherapy, a method for high voltage electric pulse assisted intratumoral chemotherapeutic drug delivery, has been accepted in the European clinics as an efficient palliative treatment for the metastatic surface tumours [2]. Calcium ion delivery via electroporation has been recently suggested as a chemotherapeutic-free alternative to bleomycin or cisplatin used in conventional electrochemotherapy, reducing the cost and potential side effects of the treatment while retaining high efficiency and selectivity towards tumour cells [3]. The sudden increase in intracellular calcium concentration leads to cell death via numerous processes such as ATP depletion, increased activity of lipases and proteases, production of reactive oxygen species, the opening of non-specific pores, etc. [4]. However, the mechanism behind the calcium electroporation remains unclear to this day. The electroporation parameters, that lead to the optimal efficiency of calcium electrotransfer, also remain to be determined.[...]