2. Academic Validation
  3. Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells

Largazole Arrests Cell Cycle at G1 Phase and Triggers Proteasomal Degradation of E2F1 in Lung Cancer Cells

  • ACS Med Chem Lett. 2013 Aug 12;4(10):921-6. doi: 10.1021/ml400093y.
Li-Chuan Wu 1,  Zhe-Sheng Wen 2,  Ya-Tao Qiu 3,  Xiao-Qin Chen 2,  Hao-Bin Chen 4,  Ming-Ming Wei 1,  Zi Liu 1,  Sheng Jiang 3,  Guang-Biao Zhou 5
Affiliations

Affiliations

  • 1 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.
  • 2 Department of Thoracic Surgery, The Cancer Hospital, Sun Yat-Sen University , Guangzhou 510080, China.
  • 3 Guangzhou Institute of Biomedicine and Health, Chinese Academy of Sciences , Guangzhou 510530, China.
  • 4 Department of Pathology, The First People's Hospital of Qu Jing , Qu Jing, Yuannan Province 655000, China.
  • 5 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.
PMID: 24900585 DOI: 10.1021/ml400093y
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.

Keywords

E2F1; Lung cancer; cell cycle; degradation; largazole.

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