2. Academic Validation
  3. NSC 95397 Suppresses Proliferation and Induces Apoptosis in Colon Cancer Cells through MKP-1 and the ERK1/2 Pathway

NSC 95397 Suppresses Proliferation and Induces Apoptosis in Colon Cancer Cells through MKP-1 and the ERK1/2 Pathway

  • Int J Mol Sci. 2018 May 31;19(6):1625. doi: 10.3390/ijms19061625.
Navneet Kumar Dubey 1 2,  Bou-Yue Peng 3 4,  Chien-Min Lin 5,  Peter D Wang 6 7,  Joseph R Wang 8,  Chun-Hao Chan 9 10,  Hong-Jian Wei 11 12,  Win-Ping Deng 13 14
Affiliations

Affiliations

  • 1 Ceramics and Biomaterials Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh 700000, Vietnam. navneet.kumar.dubey@tdt.edu.vn.
  • 2 Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh 700000, Vietnam. navneet.kumar.dubey@tdt.edu.vn.
  • 3 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. pemg@tmu.edu.tw.
  • 4 Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan. pemg@tmu.edu.tw.
  • 5 Department of Neurosurgery, Taipei Medical University⁻Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei 235, Taiwan. m513092004@tmu.edu.tw.
  • 6 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. dpw1@tmu.edu.tw.
  • 7 Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan. dpw1@tmu.edu.tw.
  • 8 Department of Periodontics, College of Dental Medicine, Columbia University, New York, NY 10032, USA. jrw2166@cumc.columbia.edu.
  • 9 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. harry811003@gmail.com.
  • 10 Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. harry811003@gmail.com.
  • 11 Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. hjwei@tmu.edu.tw.
  • 12 School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. hjwei@tmu.edu.tw.
  • 13 School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. wpdeng@tmu.edu.tw.
  • 14 Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. wpdeng@tmu.edu.tw.
PMID: 29857489 DOI: 10.3390/ijms19061625
Abstract

NSC 95397, a quinone-based small molecule compound, has been identified as an inhibitor for dual-specificity phosphatases, including mitogen-activated protein kinase phosphatase-1 (MKP-1). MKP-1 is known to inactivate mitogen-activated protein kinases by dephosphorylating both of their threonine and tyrosine residues. Moreover, owing to their participation in tumorigenesis and drug resistance in colon Cancer cells, MKP-1 is an attractive therapeutic target for colon Cancer treatment. We therefore investigated the inhibitory activity of NSC 95397 against three colon Cancer cell lines including SW480, SW620, and DLD-1, and their underlying mechanisms. The results demonstrated that NSC 95397 reduced cell viability and anchorage-independent growth of all the three colon Cancer cell lines through inhibited proliferation and induced Apoptosis via regulating cell-cycle-related proteins, including p21, cyclin-dependent kinases, and caspases. Besides, by using mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) inhibitor U0126, we provided mechanistic evidence that the antineoplastic effects of NSC 95397 were achieved via inhibiting MKP-1 activity followed by ERK1/2 phosphorylation. Conclusively, our results indicated that NSC 95397 might serve as an effective therapeutic intervention for colon Cancer through regulating MKP-1 and ERK1/2 pathway.

Keywords

ERK1/2; MKP-1; NSC 95397; antiproliferation; apoptosis; colon cancer.

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