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.
Original language | English |
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Article number | 1625 |
Journal | International Journal of Molecular Sciences |
Volume | 19 |
Issue number | 6 |
DOIs | |
Publication status | Published - Jun 1 2018 |
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Keywords
- Antiproliferation
- Apoptosis
- Colon cancer
- ERK1/2
- MKP-1
- NSC 95397
ASJC Scopus subject areas
- Catalysis
- Molecular Biology
- Spectroscopy
- Computer Science Applications
- Physical and Theoretical Chemistry
- Organic Chemistry
- Inorganic Chemistry
Cite this
NSC 95397 suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and the ERK1/2 pathway. / Dubey, Navneet Kumar; Peng, Bou Yue; Lin, Chien Min; Wang, Peter D.; Wang, Joseph R.; Chan, Chun Hao; Wei, Hong Jian; Deng, Win Ping.
In: International Journal of Molecular Sciences, Vol. 19, No. 6, 1625, 01.06.2018.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - NSC 95397 suppresses proliferation and induces apoptosis in colon cancer cells through MKP-1 and the ERK1/2 pathway
AU - Dubey, Navneet Kumar
AU - Peng, Bou Yue
AU - Lin, Chien Min
AU - Wang, Peter D.
AU - Wang, Joseph R.
AU - Chan, Chun Hao
AU - Wei, Hong Jian
AU - Deng, Win Ping
PY - 2018/6/1
Y1 - 2018/6/1
N2 - 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.
AB - 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.
KW - Antiproliferation
KW - Apoptosis
KW - Colon cancer
KW - ERK1/2
KW - MKP-1
KW - NSC 95397
UR - http://www.scopus.com/inward/record.url?scp=85047941952&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=85047941952&partnerID=8YFLogxK
U2 - 10.3390/ijms19061625
DO - 10.3390/ijms19061625
M3 - Article
AN - SCOPUS:85047941952
VL - 19
JO - International Journal of Molecular Sciences
JF - International Journal of Molecular Sciences
SN - 1661-6596
IS - 6
M1 - 1625
ER -