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

Experimental and Therapeutic Medicine
Yuanxin ZhangWei Shi

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.

Methods Mentioned

BETA
fluorescence microscopy
PCR
Flow Cytometry
Protein Assay

Software Mentioned

SPSS
ImageJ
Flowjo

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