IC-4, a new irreversible EGFR inhibitor, exhibits prominent anti-tumor and anti-angiogenesis activities
- Authors
- Li, Y.B., Wang, Z.Q., Yan, X., Chen, M.W., Bao, J.L., Wu, G.S., Ge, Z.M., Zhou, D.M., Wang, Y.T., and Li, R.T.
- ID
- ZDB-PUB-130726-10
- Date
- 2013
- Source
- Cancer letters 340(1): 88-96 (Journal)
- Registered Authors
- Keywords
- irreversible TKI, EGFR, angiogenesis, breast cancer
- MeSH Terms
-
- Angiogenesis Inhibitors/pharmacology*
- Animals
- Antineoplastic Agents/pharmacology
- Breast Neoplasms/drug therapy*
- Cell Cycle/drug effects
- Cell Line, Tumor/drug effects
- Cell Movement/drug effects
- Cell Proliferation/drug effects
- Cell Survival/drug effects
- Drug Screening Assays, Antitumor
- Embryo, Nonmammalian/blood supply
- Embryo, Nonmammalian/drug effects
- Female
- Human Umbilical Vein Endothelial Cells/drug effects
- Human Umbilical Vein Endothelial Cells/physiology
- Humans
- Neovascularization, Physiologic/drug effects
- Phosphorylation
- Protein Kinase Inhibitors/pharmacology
- Protein Processing, Post-Translational/drug effects*
- Thiocarbamates/pharmacology*
- Zebrafish
- PubMed
- 23856030 Full text @ Cancer Lett.
Accumulating evidence suggested that the irreversible tyrosine kinase inhibitors (TKIs) have potential to override the acquired resistance to target-based therapies. Herein, we reported IC-4 as a novel irreversible TKI for epidermal growth factor receptor (EGFR). IC-4 potentially suppressed proliferation, induced apoptosis and a G2/M cell cycle arrest in breast cancer cells, correlating with inhibition of EGF-induced EGFR activation, but independent of DNA damage. In addition, IC-4 exhibited anti-angiogenetic activities both in vitro and in vivo. It suppressed cell viability and proliferation induced by various growth factors in human umbilical vein endothelial cells (HUVECs). IC-4 also inhibited HUVECs migration and tube formation. In transgenic zebrafish embryo model, IC-4 was shown to suppress formation of intersegmental vessel and development of subintestinal vessels. Taken together, these results demonstrated that IC-4 is a new irreversible EGFR-TKI, exhibiting potent anti-breast cancer and anti-angiogenetic effects.