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Cited by 41Cancer Mechanisms and TherapyProtein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancer

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Src family kinase inhibitor PP2 efficiently inhibits cervical cancer cell proliferation through down-regulating phospho-Src-Y416 and phospho-EGFR-Y1173

Kong, Lu, Deng, Zhihong, Shen, Haiying, Zhang, Yuxiang·2011·Molecular and Cellular Biochemistry
DOI 10.1007/s11010-010-0632-1
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Abstract

Tyrosine (Y) kinases inhibitors have been approved for targeted treatment of cancer. However, their clinical use is limited to some cancers and the mechanism of their action remains unclear. Previous study has indicated that PP2, a selective inhibitor of the Src family of non-receptor tyrosine kinases (nRTK), efficiently repressed cervical cancer growth in vitro and in vivo. In this regard, our aims are to explore the mechanism of PP2 on cervical cancer cell growth inhibition by investigating the suppressive divergence among PP1, PP2, and a negative control compound PP3. MTT results showed that three compounds had different inhibitory effects on proliferation of two cervical cancer cells, HeLa and SiHa, and PP2 was most efficient in a time- and dose-dependent manner. Moreover, we found 10 μM PP2 down-regulated pSrc-Y416 (P < 0.05), pEGFR-Y845 (P < 0.05), and -Y1173 (P < 0.05) expression levels, while 10 μM PP1 down-regulated pSrc-Y416 (P < 0.05) and pEGFR-Y845 (P < 0.05), but not pEGFR-Y1173; 10 μM PP3 down-regulated only pEGFR-Y1173 (P < 0.05). PP2 could modulate cell cycle arrest by up-regulating p21(Cip1) and p27(Kip1) in both HeLa and SiHa cells and down-regulating expression of cyclin A, and cyclin dependent kinase-2, -4 (Cdk-2, -4) in HeLa and of cyclin B and Cdk-2 in SiHa. Our results indicate that Src pathway and EGFR pathway play different roles in the proliferation of cervical cancer cells and PP2 efficiently reduces cervical cancer cell proliferation by reduction o…

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Cited by

Metadata

Authors
Kong, L., Deng, Z., Shen, H., & Zhang, Y.
Affiliations
Capital Medical University (CN)
Corresponding author
Zhang, Yuxiang
ORCID
Venue
Molecular and Cellular Biochemistry
Publisher
Springer Science and Business Media LLC
Published
2010-11-04
Volume
348
Issue
1-2
Pages
11-19
ISSN
  • 0300-8177 (ISSN-L)
  • 1573-4919
DOI
10.1007/s11010-010-0632-1
OpenAlex
W2005363728
Cited by
41
References
0
Citations by year
2026: 3 · 2025: 1 · 2022: 5 · 2021: 1 · 2019: 3 · 2018: 2 · 2017: 3 · 2016: 5 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 5
FWCI
2.60
Type
journal article
Language
en
Open access
closed
Licence
www.springer.com/tdm (tdm)
Locations
  • Molecular and Cellular Biochemistry (publishedVersion)
  • PubMed (publishedVersion)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer Mechanisms and Therapy
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › PI3K/AKT/mTOR signaling in cancer
Keywords
PP2, Src family kinase inhibitor, cervical cancer, cell proliferation, EGFR, Src kinase, non-receptor tyrosine kinase, protein phosphatase 1, cell cycle arrest, p21, p27, cyclin-dependent kinases, HeLa cells, SiHa cells
MeSH terms
Antineoplastic Agents, Cell Cycle, Uterine Cervical Neoplasms, Dose-Response Relationship, Drug, Female, HeLa Cells, Humans, Phosphorylation, Pyrazoles, Pyrimidines, Time Factors, Signal Transduction, Cell Cycle Proteins, src-Family Kinases, Protein Kinase Inhibitors, Cell Proliferation, ErbB Receptors

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