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

International Journal of Molecular Sciences

NavneetKumar Dubey¹  Chien-Min Lin²  JosephR. Wang³  Chun-Hao Chan⁴  Win-Ping Deng⁴  PeterD. Wang⁴  Bou-Yue Peng⁴  Hong-Jian Wei⁵ 

[1] Ceramics and Biomaterials Research Group, Advanced Institute of Materials Science, Ton Duc Thang University, Ho Chi Minh 700000, Vietnam;Department of Neurosurgery, Taipei Medical University–Shuang Ho Hospital, Ministry of Health and Welfare, New Taipei 235, Taiwan;Department of Periodontics, College of Dental Medicine, Columbia University, New York, NY 10032, USA;School of Dentistry, College of Oral Medicine, Taipei Medical University, Taipei 110, Taiwan;Stem Cell Research Center, Taipei Medical University, Taipei 110, Taiwan;

关键词: NSC 95397;    MKP-1;    ERK1/2;    colon cancer;    antiproliferation;    apoptosis;   

DOI  :  10.3390/ijms19061625

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown