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CC-5079: A Small Molecule with MKP1, Antiangiogenic, and Antitumor Activity
- Source :
-
Journal of Surgical Research . Nov2010, Vol. 164 Issue 1, p116-125. 10p. - Publication Year :
- 2010
-
Abstract
- Introduction: CC-5079, a small molecule inhibitor of tubulin polymerization and phosphodiesterase-4 activity, was evaluated for antiangiogenic and antitumor activities. Materials and Methods: First, CC-5079 in vitro activity on human umbilical vein endothelial cells (HUVECs), fibroblasts, and MC38 were evaluated by proliferation, migration, and invasion assays. Second, CC-5079 effect on microvessel formation was evaluated ex vivo by chick chorioallantoic membrane (CAM), rat aortic rings assays, and with directed in vivo angiogenesis assay (DIVAA). Third, CC-5079 antitumor effect was determined in treatment of C57BL/6 mice with MC38 tumors. Finally, CC-5079 modulation of MKP1 in HUVECs, human fibroblast, and MC38 were determined by RNA isolation for qRT-PCR. Results: At the 0.1 μM concentration CC-5079 significantly inhibited HUVEC, fibroblast, and MC38 proliferation and migration (all P < 0.001). At the 0.1 μM concentration, CC-5079 also inhibited HUVEC invasion (P < 0.05) but not fibroblast. In the CAM and rat aortic ring assays, CC-5079 at 0.1 μM inhibited microvessel formation (P < 0.05). By DIVAA, CC-5079 at 1 mg/kg/d continuous delivered inhibited microvessel formation (P < 0.05). Intraperitoneal CC-5079 was well tolerated and inhibited the growth of subcutaneous MC38 at 100 mg/kg/d (P < 0.01). By qRT-PCR, CC-5079 stimulated MKP1 expression in HUVEC and fibroblast. Conclusion: CC-5079 demonstrated stimulation of MKP1, antiangiogenic, and antitumor properties. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 00224804
- Volume :
- 164
- Issue :
- 1
- Database :
- Academic Search Index
- Journal :
- Journal of Surgical Research
- Publication Type :
- Academic Journal
- Accession number :
- 54488915
- Full Text :
- https://doi.org/10.1016/j.jss.2009.01.031