Conjugated Linoleic Acid Strengthens the Apoptotic Effect of Cisplatin in A549 Cells

Abstract

One of the chemotherapeutic agents widely used in the treatment of non-small cell lung cancer (NSCLC) is cisplatin. However, the resistance of cancer cells to cisplatin and additionally serious side effects from cisplatin limit its use. Conjugated linoleic acid (CLA) has been shown to suppress the development of carcinogenesis in vitro and in vivo studies and has antitumoral activity in many cancers. The study aimed to investigate the potential effect of using cisplatin, the first-line treatment for NSCLC, in combination with CLA to increase its efficacy in low-dose use. MTT cytotoxicity assay was performed to determine the effects of CLA in combination with cisplatin on cell viability of NSCLC cell lines. The apoptotic effect of this combination on NSCLC cell lines and cell cycle distribution was determined by flow cytometry. At the same time, apoptosis and cell cycle-related gene expression levels were determined by Real-Time PCR. Combination treatment of low-dose cisplatin with CLA resulted in a significant decrease in cell viability compared to cisplatin alone, and an increase in the rate of apoptotic cells was observed. While cisplatin caused G1 phase arrest in cancer cells, there was an increase in cell percentages in S and G2 phases after combined application with CLA. In high-dose cisplatin administration, it was observed that the efficiency of the decrease in anti-apoptotic BCL2 expression related to resistance to chemotherapeutic agents was less than that of low-dose cisplatin administration. Combined administration of high-dose cisplatin with CLA significantly recovered BCL2 downregulation.