Characterization of Antitumor Activity of a Synthetic Moronecidin-Like Peptide Computationally Predicted from the Tiger Tail Seahorse Hippocampus Comes in Tumor-bearing Mice

Abstract

Breast cancer is one of the well-known non-cutaneous cancers among women worldwide. In the present study, we have characterized the anti-cancer activity of Moronecidin-like peptide derived from the Hippocampus comes in comparison with a well-known antimicrobial peptide (AMP), Piscidin. Evaluation of the cytotoxic activity of the peptides against 4T1 cancer cells and bone marrow-derived dendritic cells (BMDCs) using MTT assay and flow cytometry demonstrated a concentration-dependent cytotoxicity of Moronecidin-like and Piscidin peptides on the viability of 4T1 cells. Among AMPs, Piscidin indicated greater cytotoxicity than Moronecidin-like against 4T1 and BMDCs. Flow cytometry data demonstrated that AMPs induced (particularly Moronecidin-like) higher level of CCR7 and CD86 compared to Non-AMP. Furthermore, the findings demonstrated an inverse relationship between the cytotoxic activity of AMPs against BMDCs and the expression of activation markers (CCR7 and CD86) on BMDCs. Measuring of IFN-gamma CD8 double-positive T-cells response demonstrated a higher frequency of IFN-gamma CD8 double-positive T-cells in mice receiving Moronecidin-like compared to those receiving Piscidin. The tumor volumes and percent survival was determined in mice bearing 4T1 orthotopic breast cancer. A significant tumor growth inhibition was observed in mice receiving AMPs (particularly Moronecidin-like) compared to those receiving PBS. Furthermore, higher percent survival was observed in mice receiving Moronecidin-like compared to the other groups. The current study suggested synthetic Moronecidin-like as an efficacious dual-functional agent that possess direct (through inducing apoptosis) and indirect (priming anticancer immune response) anticancer activity against breast cancer in mice.