2. Academic Validation
  3. Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo

Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo

  • Pharmacol Res. 2021 Nov;173:105870. doi: 10.1016/j.phrs.2021.105870.
Ying Hou 1,  Rong Liu 2,  Mengwei Xia 2,  Chong Sun 1,  Bingling Zhong 1,  Jie Yu 1,  Nana Ai 3,  Jin-Jian Lu 1,  Wei Ge 3,  Bo Liu 4,  Xiuping Chen 5
Affiliations

Affiliations

  • 1 Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
  • 2 Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China.
  • 3 Centre of Reproduction, Development and Aging (CRDA), Faculty of Health Sciences, University of Macau, Taipa, Macau, China.
  • 4 Key Laboratory of Green Chemistry & Technology of Ministry of Education, College of Chemistry, Sichuan University, Chengdu 610064, China. Electronic address: chembliu@scu.edu.cn.
  • 5 Institute of Chinese Medical Sciences, University of Macau, Taipa, Macau, China; Department of Pharmaceutical Sciences, Faculty of Health Sciences, University of Macau, Taipa, Macau, China. Electronic address: xpchen@um.edu.mo.
PMID: 34500061 DOI: 10.1016/j.phrs.2021.105870
Abstract

Colorectal Cancer (CRC) is one of the most common causes of cancer-related death worldwide. Nannocystin ax (NAN), a 21-membered cyclodepsipeptide initially isolated from myxobacteria of the Nannocystis genus, was found to target the eukaryotic elongation factor 1A (eEF1A). The current study was designed to evaluate the Anticancer effect and underlying mechanisms of NAN with in vitro and in vivo models. Results showed that NAN induced G1 phase cell cycle arrest and caspase-independent Apoptosis in HCT116 and HT29 human CRC cells. NAN significantly downregulated cyclin D1 level in a short time, but NAN did not affect the transcription level and ubiquitin-dependent degradation of cyclin D1. Furthermore, NAN treatment directly targeted eEF1A and partially decreased the synthesis of new proteins, contributing to the downregulation of cyclin D1. Besides, NAN significantly suppressed tumor growth in the zebrafish xenograft model. In conclusion, NAN triggered G1 phase cell cycle arrest through cyclin D1 downregulation and eEF1A-targeted translation inhibition and promoted caspase-independent Apoptosis in CRC cells.

Keywords

Apoptosis; Cyclin D1; G1 cell cycle arrest; Nannocystin ax.

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