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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
  • View Affiliations / Copyright

    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
    Copyright: © Bai et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Article Number: 294
    |
    Published online on: September 25, 2020
       https://doi.org/10.3892/ol.2020.12157
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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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1 

Siegel RL, Miller KD, Goding Sauer A, Fedewa SA, Butterly LF, Anderson JC, Cercek A, Smith RA and Jemal A: Colorectal cancer statistics, 2020. CA Cancer J Clin. 70:145–164. 2020. View Article : Google Scholar : PubMed/NCBI

2 

Miller KD, Nogueira L, Mariotto AB, Rowland JH, Yabroff KR, Alfano CM, Jemal A, Kramer JL and Siegel RL: Cancer treatment and survivorship statistics, 2019. CA Cancer J Clin. 69:363–385. 2019. View Article : Google Scholar : PubMed/NCBI

3 

Evan GI and Vousden KH: Proliferation, cell cycle and apoptosis in cancer. Nature. 411:342–348. 2001. View Article : Google Scholar : PubMed/NCBI

4 

Van der Jeught K, Xu HC, Li YJ, Lu XB and Ji G: Drug resistance and new therapies in colorectal cancer. World J Gastroenterol. 24:3834–3848. 2018. View Article : Google Scholar

5 

Vidimar V, Licona C, Cerón-Camacho R, Guerin E, Coliat P, Venkatasamy A, Ali M, Guenot D, Le Lagadec R, Jung AC, et al: A redox ruthenium compound directly targets PHD2 and inhibits the HIF1 pathway to reduce tumor angiogenesis independently of p53. Cancer Lett 440–441. 145–155. 2019. View Article : Google Scholar

6 

Tripodi F, Dapiaggi F, Orsini F, Pagliarin R, Sello G and Coccetti P: Synthesis and biological evaluation of new 3-amino-2-azetidinone derivatives as anti-colorectal cancer agents. MedChemComm. 9:843–852. 2018. View Article : Google Scholar : PubMed/NCBI

7 

Zhu H, Zhang L, Wu S, Teraishi F, Davis JJ, Jacob D and Fang B: Induction of S-phase arrest and p21 overexpression by a small molecule 2[[3-(2,3-dichlorophenoxy)propyl] amino]ethanol in correlation with activation of ERK. Oncogene. 23:4984–4992. 2004. View Article : Google Scholar : PubMed/NCBI

8 

Hartwell LH and Kastan MB: Cell cycle control and cancer. Science. 266:1821–1828. 1994. View Article : Google Scholar : PubMed/NCBI

9 

Mirza-Aghazadeh-Attari M, Darband SG, Kaviani M, Mihanfar A, Aghazadeh Attari J, Yousefi B and Majidinia M: DNA damage response and repair in colorectal cancer: Defects, regulation and therapeutic implications. DNA Repair (Amst). 69:34–52. 2018. View Article : Google Scholar : PubMed/NCBI

10 

Zhang B, Cui B, Du J, Shen X, Wang K, Chen J, Xiao L, Sun C and Li Y: ATR activated by EB virus facilitates chemotherapy resistance to cisplatin or 5-fluorouracil in human nasopharyngeal carcinoma. Cancer Manag Res. 11:573–585. 2019. View Article : Google Scholar : PubMed/NCBI

11 

Liu FY, Wu YH, Zhou SJ, Deng YL, Zhang ZY, Zhang EL and Huang ZY: Minocycline and cisplatin exert synergistic growth suppression on hepatocellular carcinoma by inducing S phase arrest and apoptosis. Oncol Rep. 32:835–844. 2014. View Article : Google Scholar : PubMed/NCBI

12 

Yao J, Huang A, Zheng X, Liu T, Lin Z, Zhang S, Yang Q, Zhang T and Ma H: 53BP1 loss induces chemoresistance of colorectal cancer cells to 5-fluorouracil by inhibiting the ATM-CHK2-P53 pathway. J Cancer Res Clin Oncol. 143:419–431. 2017. View Article : Google Scholar : PubMed/NCBI

13 

Shen T and Huang S: The role of Cdc25A in the regulation of cell proliferation and apoptosis. Anticancer Agents Med Chem. 12:631–639. 2012. View Article : Google Scholar : PubMed/NCBI

14 

Ciccia A and Elledge SJ: The DNA damage response: Making it safe to play with knives. Mol Cell. 40:179–204. 2010. View Article : Google Scholar : PubMed/NCBI

15 

Kuo LJ and Yang LX: Gamma-H2AX - a novel biomarker for DNA double-strand breaks. In Vivo. 22:305–309. 2008.PubMed/NCBI

16 

Zhang X, Huang Q, Wang X, Xu Y, Xu R, Han M, Huang B, Chen A, Qiu C, Sun T, et al: Bufalin enhances radiosensitivity of glioblastoma by suppressing mitochondrial function and DNA damage repair. Biomed Pharmacother. 94:627–635. 2017. View Article : Google Scholar : PubMed/NCBI

17 

Shin SY, Ahn S, Koh D and Lim Y: p53-dependent and -independent mechanisms are involved in (E)-1-(2-hydroxyphenyl)-3-(2-methoxynaphthalen-1-yl)prop-2-en-1-one (HMP)-induced apoptosis in HCT116 colon cancer cells. Biochem Biophys Res Commun. 479:913–919. 2016. View Article : Google Scholar : PubMed/NCBI

18 

DE Wever O, Sobczak-Thépot J, Vercoutter-Edouart AS, Michalski JC, Ouelaa-Benslama R, Stupack DG, Bracke M, Wang JYJ, Gespach C and Emami S: Priming and potentiation of DNA damage response by fibronectin in human colon cancer cells and tumor-derived myofibroblasts. Int J Oncol. 39:393–400. 2011.

19 

Solier S, Zhang YW, Ballestrero A, Pommier Y and Zoppoli G: DNA damage response pathways and cell cycle checkpoints in colorectal cancer: Current concepts and future perspectives for targeted treatment. Curr Cancer Drug Targets. 12:356–371. 2012. View Article : Google Scholar : PubMed/NCBI

20 

William-Faltaos S, Rouillard D, Lechat P and Bastian G: Cell cycle arrest and apoptosis induced by oxaliplatin (L-OHP) on four human cancer cell lines. Anticancer Res. 26((3A)): 2093–2099. 2006.PubMed/NCBI

21 

Voland C, Bord A, Péleraux A, Pénarier G, Carrière D, Galiègue S, Cvitkovic E, Jbilo O and Casellas P: Repression of cell cycle-related proteins by oxaliplatin but not cisplatin in human colon cancer cells. Mol Cancer Ther. 5:2149–2157. 2006. View Article : Google Scholar : PubMed/NCBI

22 

Fang Y, Yu H, Liang X, Xu J and Cai X: Chk1-induced CCNB1 overexpression promotes cell proliferation and tumor growth in human colorectal cancer. Cancer Biol Ther. 15:1268–1279. 2014. View Article : Google Scholar : PubMed/NCBI

23 

Greenow KR, Clarke AR, Williams GT and Jones R: Wnt-driven intestinal tumourigenesis is suppressed by Chk1 deficiency but enhanced by conditional haploinsufficiency. Oncogene. 33:4089–4096. 2014. View Article : Google Scholar : PubMed/NCBI

24 

Liu X, Bian C, Ren K, Jin H, Li B and Shao RG: Lidamycin induces marked G2 cell cycle arrest in human colon carcinoma HT-29 cells through activation of p38 MAPK pathway. Oncol Rep. 17:597–603. 2007.PubMed/NCBI

25 

Soule BP, Simone NL, DeGraff WG, Choudhuri R, Cook JA and Mitchell JB: Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines. Radiat Oncol. 5:82010. View Article : Google Scholar : PubMed/NCBI

26 

Xiao Z, Xue J, Sowin TJ, Rosenberg SH and Zhang H: A novel mechanism of checkpoint abrogation conferred by Chk1 downregulation. Oncogene. 24:1403–1411. 2005. View Article : Google Scholar : PubMed/NCBI

27 

Pauklin S, Kristjuhan A, Maimets T and Jaks V: ARF and ATM/ATR cooperate in p53-mediated apoptosis upon oncogenic stress. Biochem Biophys Res Commun. 334:386–394. 2005. View Article : Google Scholar : PubMed/NCBI

28 

Wu S, Zhu H, Gu J, Zhang L, Teraishi F, Davis JJ, Jacob DA and Fang B: Induction of apoptosis and down-regulation of Bcl-XL in cancer cells by a novel small molecule, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol. Cancer Res. 64:1110–1113. 2004. View Article : Google Scholar : PubMed/NCBI

29 

Carrassa L and Damia G: DNA damage response inhibitors: Mechanisms and potential applications in cancer therapy. Cancer Treat Rev. 60:139–151. 2017. View Article : Google Scholar : PubMed/NCBI

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Copy and paste a formatted citation
Spandidos Publications style
Bai B, Shan L, Wang J, Hu J, Zheng W, Lv Y, Chen K, Xu D and Zhu H: Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells. Oncol Lett 20: 294, 2020.
APA
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y. ... Zhu, H. (2020). Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells. Oncology Letters, 20, 294. https://doi.org/10.3892/ol.2020.12157
MLA
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y., Chen, K., Xu, D., Zhu, H."Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells". Oncology Letters 20.6 (2020): 294.
Chicago
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y., Chen, K., Xu, D., Zhu, H."Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells". Oncology Letters 20, no. 6 (2020): 294. https://doi.org/10.3892/ol.2020.12157
Copy and paste a formatted citation
x
Spandidos Publications style
Bai B, Shan L, Wang J, Hu J, Zheng W, Lv Y, Chen K, Xu D and Zhu H: Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells. Oncol Lett 20: 294, 2020.
APA
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y. ... Zhu, H. (2020). Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells. Oncology Letters, 20, 294. https://doi.org/10.3892/ol.2020.12157
MLA
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y., Chen, K., Xu, D., Zhu, H."Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells". Oncology Letters 20.6 (2020): 294.
Chicago
Bai, B., Shan, L., Wang, J., Hu, J., Zheng, W., Lv, Y., Chen, K., Xu, D., Zhu, H."Small molecule 2,3‑DCPE induces S phase arrest by activating the ATM/ATR‑Chk1‑Cdc25A signaling pathway in DLD‑1 colon cancer cells". Oncology Letters 20, no. 6 (2020): 294. https://doi.org/10.3892/ol.2020.12157
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