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 lc3b. the anti-autophagic and anti-cancer effects of these novel peptides were examined in breast cancer mcf7 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 lc3b and p62/sqstm1. data were analyzed using student’s t-test by microsoft excel 2016.results: one of synthetized peptides (lirm2) could efficiently disrupt autophagy (lc3b and p62 levels) in mcf7 cells compared with a scramble peptide. then, the cells were exposed to different concentrations of lirm2, alone and in combination with 5-fu, for 24 h and 48 h. the results indicated that lirm2 up to200 µg/ml did not dramatically change cancer cell growth, while its combination could enhance cytotoxic effects of chemotherapy with 5-fu in mcf7 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.