Effect of aconitine-containing agent BC1 upon electrokinetic characteristics of tumor cells

Abstract

Earlier it has been shown, that aconitine-containing agent BC1 in noncytotoxic concentration is capable to cause inversion of a surface charge of endothelial cells that can result in inhibition of tumor vascularization and tumor growth. In vivo BC1 does not show anticancer action against Lewis lung carcinoma (LLC) while it is highly effective against its low-metastatic counterpart LLC/R9. Different anticancer efficacy of BC1 against LLC and LLC/R9 can be related to the different sensitivity of tumor cells. As voltage-gated sodium channels are the basic molecular target of aconitine alkaloid action, the purpose of the work was the comparative study of the influence of BC1 on electrokinetic characteristics of LLC and LLC/R9 cells as the possible mechanism of its anticancer action. LLC and LLC/R9 cells were incubated during 48 hours in a complete culture medium containing various concentrations of BC1, and linear speed of tumor cell movement in a constant electric field with an intensity of 20 V/sm in 0,1 M phosphatic buffer at pH 7,0 and t=27°C was measured. It was found, that 100% of tumor cells (independently on BC1 concentrations) showed electrophoretic mobility and had a negative surface charge. In the absence of BC1 ζ- potential distribution of LLC/R9 cells was characterized by shift (in comparison with LLC cells) towards lower values. BC1 caused a reduction of C-potential and the absolute value of the surface charge density of LLC/R9 cells of about 20-30% and did not influence the surface charge of LLC cells. Since the decrease in surface charge can cause tumor cell death or redifferentiation, the anticancer activity of BC1 against LLC/R9 can be associated with BC1-induced changes in the surface charge of tumor cells.