Apoptosis inducing potential of Cyclosporine C in human lung cancer cells (A549)

Cyclotides are a large group of plant based cyclic peptides that have attracted attention in the field of peptide drug design. Cyclic peptides exhibit a more potent biological activity when compared to linear peptides due to their stable cyclic structure. Cyclosporine C is a naturally occurring lipophilic cyclic peptide which is used as an immunosuppressant drug. The objective of this study was to establish Cyclosporine C as a viable novel anticancer drug in the treatment of lung cancer and to . find the optimal concentration at which Cyclosporine C results in a significant decrease of viable cancer cells to determine the physiological changes caused by Cyclosporine C and also to find the pathway of apoptosis that is induced by Cyclosporine C. The cytotoxic effect of Cyclosporine C was assessed using techniques such as Mll, Hoechst staining, DNA fragmentation, Flowcytometry and Western blot which were carried out on Lung adenocarcinoma cell line A549. The results obtained showed a significant decrease in A549 viable cells at a concentration of 200 mu g/mL of Cyclosporine C as observed by the MTT assay. The nuclear condensation and DNA fragmentation of apoptotic cells were observed using Hoechst 33258 staining and DNA fragmentation assays respectively. Western blot confirms that Cyclosporine C treated cells expressed a significant level of caspase-9 enzyme. From the results obtained, we can conclude that Cyclosporine C induces apoptosis in Lung adenocarcinoma cell line A549. The apoptosis is induced by caspace-9 enzyme dependent pathway. The antitumor activity of Cyclosporine C suggests that it has potential as a novel anticancer drug for human lung cancer treatment.