Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells

Bai,Bingjun; Shan,Lina; Wang,Jianhong; Hu,Jinhui; Zheng,Wenqian; Lv,Yiming; Chen,Kangke; Xu,Dengyong; Zhu,Hongbo

doi:10.3892/ol.2020.12157

Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells

Authors:
- Bingjun Bai
- Lina Shan
- Jianhong Wang
- Jinhui Hu
- Wenqian Zheng
- Yiming Lv
- Kangke Chen
- Dengyong Xu
- Hongbo Zhu
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Affiliations: Department of Colorectal Surgery, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310016, P.R. China, Department of Colorectal Surgery, Deqing People's Hospital/Deqing Campus, Sir Run Run Shaw Hospital, Huzhou, Zhejiang 313216, P.R. China
Published online on: September 25, 2020 https://doi.org/10.3892/ol.2020.12157
Article Number: 294
Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

In our previous study, it was reported that 2[[3‑(2,3‑dichlorophenoxy)propyl]amino]ethanol (2,3‑DCPE) induces apoptosis and cell cycle arrest. The current study aimed to investigate the molecular mechanism involved in 2,3‑DCPE‑induced S phase arrest. The results demonstrated that 2,3‑DCPE upregulated phosphorylated (p‑)H2A histone family member X, a biomarker of DNA damage, in the DLD‑1 colon cancer cell line. Western blotting revealed that 2,3‑DCPE increased the checkpoint kinase (Chk)1 (Ser317 and Ser345) level and decreased the expression of M‑phase inducer phosphatase 1 (Cdc25A) in a time‑dependent manner. Subsequently, the results demonstrated that the ataxia‑telangiectasia mutated (ATM) and ataxia‑telangiectasia and Rad3‑related (ATR) inhibitors wortmannin and caffeine had no effect on the cell cycle; however, the inhibitors partially abrogated 2,3‑DCPE‑induced S phase arrest. Flow cytometry assays revealed that caffeine (2 mM) reduced the proportion of S phase cells from 83 to 39.6% and that wortmannin (500 nM) reduced the proportion of S phase cells from 83 to 48.2%. Furthermore, wortmannin and caffeine inhibited the 2,3‑DCPE‑mediated phosphorylation of Chk1 and the degradation of Cdc25A. However, these ATM/ATR inhibitors had limited effect on 2,3‑DCPE‑induced apoptosis. Taken together, the data of the current study indicated that 2,3‑DCPE caused DNA damage in colon cancer cells and that 2,3‑DCPE‑induced S phase arrest was associated with the activation of the ATM/ATR‑Chk1‑Cdc25A pathway.

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