A Preliminary Study in Search of Potential Peptide Candidates for a Combinational Therapy with Cancer Chemotherapy Drug

Abstract

Cancer which caused by the growth and spreading of abnormal cells in an uncontrolled manner remains a major cause of death affecting millions of people. The current cancer chemotherapy treatment modalities have several disadvantages, mostly related to their undesirable side effects. In this study, we explore the potencies of selected cell penetrating antimicrobial peptides in combination with the widely used chemotherapy drug, Doxorubicin (DOX), to increase the specificity of anticancer chemotherapy. Screening the potential peptide candidates to be developed into chemotherapy drug combination led to identification of two most potent peptides, Tachyplesin 1 (TCH) and Latarcin 1 (LTC). Cell viability of normal liver cells was reduced to 50% by 20 µM of TCH or LTC, while liver cancer cell lines lost 50% of their viability at approximately 4 µM of these peptides. The combination of DOX with TCH peptide showed the higher levels of lactate dehydrogenase (LDH) leakage from cancer cells (80%) compared to normal cells (30%). The combinational treatment DOX-peptide showed significant (P < 0.01) increase in caspase 3/7 activity compared to DOX alone. Pre-treatment of the cells with TCH peptides prior to DOX treatment considerably increased the Caspase 3/7 activities in both cell types with significant increase (P < 0.05) in cancer cells compared to normal cells. Our study demonstrate that TCH peptide is a potential anticancer peptide that could be used in combinational therapy with cancer chemotherapy drugs.