PUBLICATION
Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo
- Authors
- Hou, Y., Liu, R., Xia, M., Sun, C., Zhong, B., Yu, J., Ai, N., Lu, J.J., Ge, W., Liu, B., Chen, X.
- ID
- ZDB-PUB-210910-12
- Date
- 2021
- Source
- Pharmacological research 173: 105870 (Journal)
- Registered Authors
- Ai, Nana, Ge, Wei
- Keywords
- Apoptosis, Cyclin D1, G1 cell cycle arrest, Nannocystin ax
- MeSH Terms
-
- Animals
- Antineoplastic Agents/pharmacology
- Antineoplastic Agents/therapeutic use*
- Apoptosis/drug effects
- Caspases/metabolism
- Colonic Neoplasms/drug therapy*
- Colonic Neoplasms/genetics
- Colonic Neoplasms/metabolism
- Cyclin D1/genetics
- Cyclin D1/metabolism
- Depsipeptides/pharmacology
- Depsipeptides/therapeutic use*
- Down-Regulation/drug effects
- G1 Phase Cell Cycle Checkpoints/drug effects
- HCT116 Cells
- HT29 Cells
- Humans
- Membrane Potential, Mitochondrial/drug effects
- Peptide Elongation Factor 1/genetics
- Zebrafish
- PubMed
- 34500061 Full text @ Pharmacol. Res.
Citation
Hou, Y., Liu, R., Xia, M., Sun, C., Zhong, B., Yu, J., Ai, N., Lu, J.J., Ge, W., Liu, B., Chen, X. (2021) Nannocystin ax, an eEF1A inhibitor, induces G1 cell cycle arrest and caspase-independent apoptosis through cyclin D1 downregulation in colon cancer in vivo. Pharmacological research. 173:105870.
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.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping