Small molecule CDS-3078 induces G<sub>2</sub>/M phase arrest and mitochondria-mediated apoptosis in HeLa cells

Zhang,Yuanxin; Li,Pengcheng; Rong,Jiamin; Ge,Yakun; Hu,Chenming; Bai,Xu; Shi,Wei

doi:10.3892/etm.2020.9414

Small molecule CDS-3078 induces G₂/M phase arrest and mitochondria-mediated apoptosis in HeLa cells

Authors:
- Yuanxin Zhang
- Pengcheng Li
- Jiamin Rong
- Yakun Ge
- Chenming Hu
- Xu Bai
- Wei Shi
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Affiliations: College of Biology and Food Engineering, Jilin Institute of Chemical Technology, Jilin, Jilin 132022, P.R. China, The Center for Combinatorial Chemistry and Drug Discovery, College of Pharmacy, Jilin University, Changchun, Jilin 130012, P.R. China, Key Laboratory for Molecular Enzymology and Engineering of The Ministry of Education, School of Life Science, Jilin University, Changchun, Jilin 130012, P.R. China
Published online on: October 29, 2020 https://doi.org/10.3892/etm.2020.9414
Article Number: 284
Copyright: © Zhang et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

The tumor suppressor p53 serves important roles in cell cycle arrest and apoptosis, and its activation increases the sensitivity of cancer cells to radiotherapy or chemotherapy. In the present study, the small molecule 2-[1-(4-(benzyloxy)phenyl)-3-oxoisoindolin-2-yl)-2-(4-methoxyphenyl)] acetic acid (CDS-3078) significantly increased p53 mRNA expression levels in a dose-dependent manner. Treatment with CDS-3078 increased p53 expression levels and p53-mediated activation of its downstream target genes in HeLa cells. Additionally, p53^+/+ HeLa cells treated with CDS-3078 presented with dysfunctional mitochondria, as indicated by the decrease in Bcl-2 levels, the increase in Bcl-2 homologous antagonist killer and the increase in cytochrome c release from the mitochondria to the cytoplasm. The present results suggested that CDS-3078 treatment significantly induced G₂/M phase cell cycle arrest. Therefore, CDS-3078 administration induced apoptosis via p53-mediated cell cycle arrest, causing mitochondrial dysfunction and resulting in apoptotic cell death in cervical cancer cells. Collectively, the present results suggested that CDS-3078 may be a potential anticancer agent.

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