title: Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells.
abstract: Aberration in cell cycle has been shown to be a common occurrence in lung cancer, and cell cycle inhibitor represents an effective therapeutic strategy. In this study, we test the effects of a natural 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 normal bronchial epithelial cells. Largazole arrests cell cycle at G1 phase with up-regulation of the expression of cyclin-dependent kinase inhibitor p21. Interestingly, largazole enhances the E2F1-HDAC1 binding affinity and induces a proteasomal degradation of E2F1, leading to suppression of E2F1 function in lung cancer but not normal 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 malignant neoplasm.
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China ; Graduate University of the Chinese Academy of Sciences , Beijing 100049, China.
authors.forename: Li-Chuan
authors.initials: LC
authors.lastname: Wu
authors.affiliation: Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University , Guangzhou 510080, China.
authors.forename: Zhe-Sheng
authors.initials: ZS
authors.lastname: Wen
authors.affiliation: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510530, China.
authors.forename: Ya-Tao
authors.initials: YT
authors.lastname: Qiu
authors.affiliation: Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University , Guangzhou 510080, China.
authors.forename: Xiao-Qin
authors.initials: XQ
authors.lastname: Chen
authors.affiliation: Department of Pathology, The First People's Hospital of Qu Jing , Qu Jing, Yuannan Province 655000, China.
authors.forename: Hao-Bin
authors.initials: HB
authors.lastname: Chen
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China ; Graduate University of the Chinese Academy of Sciences , Beijing 100049, China.
authors.forename: Ming-Ming
authors.initials: MM
authors.lastname: Wei
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China ; Graduate University of the Chinese Academy of Sciences , Beijing 100049, China.
authors.forename: Zi
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510530, China.
authors.forename: Sheng
authors.initials: S
authors.lastname: Jiang
authors.affiliation: Division of Molecular Carcinogenesis and Targeted Therapy for Cancer, State Key Laboratory of Biomembrane and Membrane Biotechnology, Institute of Zoology, Chinese Academy of Sciences , Beijing 100101, China.
authors.forename: Guang-Biao
authors.initials: GB
authors.lastname: Zhou
keywords: E2F1; Lung cancer; cell cycle; degradation; largazole