Synergistic Effects of 4-Aminopyridine and Paclitaxel on MCF 7 Cell Line

Abstract

Objectives: Aim of this study is to increase the effectiveness of paclitaxel (PTX) with the use of 4 - aminopyridine (4-AP) on breast cancer cell lineMCF-7.Methods: In this study, L-929 (ATCC CRL-6364) and MCF-7 (ATCC - HTB 22) cell lines were used. IC50 and survival values were determined bytrypan blue exclusion; cell cycle analysis was determined by measuring levels of Cdk2 and Histone (H3) and plasma membrane potential (Vm)measurements were performed using fluorescent Bis-(1,3-dibutylbarbituric acid) trimethine oxonol (DiBaC4(3)).Results: IC50 values were determined for two agents and these values were combined. Combination treatments ie. "4-AP (4 mM) + PTX (5 nM)"and "4-AP (4 mM) + PTX (7.5 nM)" decreased viability 17% ± 8.08 and 45% ± 3.18, respectively for L-929 cells and decreased viability 60%± 3.7 and74%± 2.6, respectively for MCF-7 cells. For L-929 cells, plasma membrane potential measurements resulted in depolarization for 4-AP, PTX (5 nM)and PTX (7.5 nM), and resulted in hyperpolarization for the combinations. For MCF-7 cells, plasma membrane potential measurements resulted indepolarization for 4-AP, PTX (7.5 nM) and 4-AP + PTX (5 nM), and resulted in hyperpolarization for PTX (5 nM) and 4-AP + PTX (7.5 nM). Changes ofCdk2 and H3 levels showed mostly G1 arrest for MCF 7 cells and G2/M arrest for L-929 cells.Conclusions: Combination treatments increased the cell death for MCF-7 cells. But, combination treatments didn't show synergistic effect on L-929which is accepted as a non-cancerous cell. These data showed that use of 4-AP in combination with the anticancer agent paclitaxel is a promisingapproach for cancer treatment.