Novel agents for induced apoptosis and treatment techniques in controlling breast tumor growth and progression

Introduction: Chemotherapy based on peptides are a novel approach for cancer therapy which is related to several advantages of peptide such as: low toxicity, easy to synthesis, high target specificity and others. Current research focuses on design of peptide inhibitor for lactate dehydrogenase enzyme in breast cancer cell that lead to decrease tumor cells growth and progression. Methods: In this study Peptiderive Server was used for design of peptide. The best modeled peptideWas selected using molecular docking software (CABS-dock) and then pharmacology properties of peptides was analysis by FAF Drugs3. Finally, the anti-proliferative activity of these compounds was confirmed on a MCF7 cell lines via MTT assay and also flow cytometry technique. Results and Discussion: the peptide ability to disrupt protein–protein interfaces is several attractive features when compared to small molecule. Therefore in this study we attempted to synthesize a peptide that could interference with the interaction of enzyme subunits and inhibited lactate dehydrogenase activity because the tetrameric form of enzyme play an important role in maintaining the active site geometry. Cytotoxic assay showed that the peptide could inhibit MCF-7 cancer cell growth, with an IC50 value of 60 μM. Our results indicated that, Inhibition of LDH case to inhibition of cell proliferation and induced cell death though the accumulation of reactive oxygen species (ROS) in the breast cell line. Conclusions: inhibition of LDHA by these peptide led to impaired cell survival in breast cancer cells and so, making it a compelling strategy for treating cancer.

کلیدواژه ها:

Lactate ، Breast cancer ، peptide inhibitor