A Novel Anti-cancer Peptide Extracted from Gynura pseudochina Rhizome: Cytotoxicity Dependent on Disulfide Bond Formation

Abstract

As current anticancer drugs have limitations, researchers have sought novel anti-cancer agents with high specificity and fewer side effects to normal cells. Bioactive peptides isolated from plants are of interest for their therapeutic potential and pharmaceutical development. In this study, a novel anticancer peptide, Gynurin (monomeric sequence: LNCCNLLL) was isolated and identified for the first time from the protein hydrolysate of Gynura pseudochina rhizomes. The presence of homodimeric Gynurin drastically inhibited human gastric cancer cells (KATO-III) with a greater inhibitory effect than 5-flurouracil without significant cytotoxicity of normal cells (Vero). By performing structural analysis using circular dichroism, Gynurin could form a random coil conformation with a partial helical structure in a mimic membrane model environment of 50% trifluoroethanol. However, in the presence of a reducing agent (DTT), treated Gynurin completely lost its cytotoxicity against KATO-III cells and adopted a random coil structure. Taken altogether, this study suggested that disulfide bond formation and peptide dimerization were crucial parameters for the anti-cancer activity of Gynurin. Consequently, dimeric Gynurin peptide could potentially be an effective therapeutic component for pharmaceutical development in the treatment of gastric cancer.