Lycosin-II Suppresses the Growth of Tumor Cells and Kills them Through Membrane Disruption and Apoptosis Induction

Recently, there has been a growing interest in the discovery of novel chemotherapeutic agents that have fewer side effects and are less likely to develop resistance. This study was conducted to examine the antitumor activity of lycosin-II, an antibacterial peptide isolated from the spider Lycosa singoriensis. Computational analysis revealed that lycosin-II has appropriate structural parameters (cationicity, alpha-helical conformation, amphipathicity) applicable for exhibiting antitumor activity. The results of MTT assay showed that lycosin-II possesses cytotoxicity (IC50 = 70.79 mu g/ml) against the human colorectal cancer cell line HCT 116 as these cells were killed 30 min after treatment. Lycosin-II also exhibits a dose-dependent antiproliferative effect, as assessed using MTT assay coupled with direct cell counting as a measure of cell growth. Lactate dehydrogenase leakage assay and scanning electron microscopy revealed that lycosin-II kills tumor cells through cell membrane disruption. Apoptosis assays showed that Bax proapoptotic protein expression level and caspase-3 activity were increased after lycosin-II treatment, which indicates the activation of intrinsic apoptotic pathway. Altogether, these data indicate that lycosin-II suppresses the growth of tumor cells and kills them through membrane disruption and activation of apoptosis. However, lycosin-II exerts moderate hemolytic activity, which may be a major challenge in therapeutic applications. In conclusion, lycosin-II may serve as a template for designing novel antitumor peptides with low toxicity to normal cells for chemotherapeutic applications.