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Aberration in cellselleck chemical cycle has been proven for being a typical occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic tactic. In this research, only we check the results of a organic macrocyclic depsipeptide largazole on lung cancer cells and report that this compound potently inhibits the proliferation and clonogenic activity of lung cancer cells but not ordinary bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation in the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, main to suppression of E2F1 perform in lung cancer but not typical bronchial epithelial cells. Because E2F1 is overexpressed in lung cancer tumor samples, these data indicate that largazole is an E2F1-targeting cell cycle inhibitor, which bears therapeutic potentials for this malignantPAK3 neoplasm.