New synthetic peptide inhibitors for targeting autophagy in cancer cells

Background and Aim: Autophagy is a catabolic process for marinating cell survival and homeostasis during physiological and pathological conditions, such as cancer. Autophagy manipulation (both inhibition and activation) has been proposed for more efficient anticancer therapies; yet more potent and specific modulators need to be developed. Here, we take advantages rational peptide design and synthetized new autophagy inhibitors of key autophagic protein LC۳B. The anti-autophagic and anti-cancer effects of these novel peptides were examined in breast cancer MCF۷ cells.Methods: Growth and cytotoxicity were evaluated by trypan blue exclusion test and MTT assay, respectively. Autophagy was evaluated by real time PCR and western blotting of key autophagic proteins LC۳B and p۶۲/SQSTM۱. Data were analyzed using student’s t-test by Microsoft Excel ۲۰۱۶.Results: One of synthetized peptides (LIRM۲) could efficiently disrupt autophagy (LC۳B and p۶۲ levels) in MCF۷ cells compared with a scramble peptide. Then, the cells were exposed to different concentrations of LIRM۲, alone and in combination with ۵-FU, for ۲۴ h and ۴۸ h. The results indicated that LIRM۲ up to۲۰۰ µg/ml did not dramatically change cancer cell growth, while its combination could enhance cytotoxic effects of chemotherapy with ۵-FU in MCF۷ cell line.Conclusion: We presented new potent and specific peptide mimetic inhibitors of autophagy that can potentiate the effectiveness of chemotherapy in an experimental model of cancer. These results may pave the way for introducing novel autophagy modulators for cancer therapy.

Keywords:

Autophagy , cancer , LC۳B , peptide inhibitor