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.
- 1. Ceramics and Biomaterials Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh 700000, Vietnam. [email protected].
- 2. Faculty of Applied Sciences, Ton Duc Thang University, Ho Chi Minh 700000, Vietnam. [email protected].
- 3. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 4. Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan. [email protected].
- 5. Department of Neurosurgery, Taipei Medical University⁻Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei 235, Taiwan. [email protected].
- 6. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 7. Department of Dentistry, Taipei Medical University Hospital, Taipei 110, Taiwan. [email protected].
- 8. Department of Periodontics, College of Dental Medicine, Columbia University, New York, NY 10032, USA. [email protected].
- 9. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 10. Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 11. Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 12. School of Dental Technology, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 13. School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan. [email protected].
- 14. Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan. [email protected].
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.