[Epothilone D, a microtubule-stabilizing compound, inhibits neointimal hyperplasia]
>>Vascul Pharmacol. 2007 Jul 5; [Epub ahead of print]
Epothilone D, a microtubule-stabilizing compound, inhibits neointimal hyperplasia after rat carotid artery injury by cell cycle arrest via regulation of G1-checkpoint proteins.
Kim TJ, Lim Y, Kim DW, Kwon JS, Son JH, Jin YR, Son DJ, Jung JC, Avery MA, Hong JT, Yun YP.
College of Pharmacy, Research Center for Bioresource and Health, Chungbuk National University, 12 Gaesin-Dong, Heungduk-Gu, Cheongju 361-763, Republic of Korea.
Epothilone D (Epo-D) is a paclitaxel-like microtubule-stabilizing agent that was isolated from the myxobacterium Sorangium cellulosum. Although Epo-D can inhibit proliferation in multiple tumor cell lines, the effect of Epo-D on neointimal hyperplasia after angioplasty has not been reported. The aim of the present study was to investigate the effects of Epo-D on neointimal hyperplasia using an in vivo rat carotid artery injury model. We demonstrated that local Epo-D treatment significantly reduced neointimal hyperplasia after in vivo rat carotid artery injury, and Epo-D potently inhibited DNA synthesis, cell cycle progression and cell proliferation after FBS- and PDGF-BB-stimulation; PDGF-BB has been identified as the most potent growth factor for stimulating the proliferation of activated rat aortic smooth muscle cells (RASMCs). To clarify the specific effects of Epo-D on cell cycle machinery, we examined its effects on cyclin-dependent kinase (CDK)2, CDK4, cyclin E, p27, and retinoblastoma (Rb) proteins as cell cycle-related proteins in cellular lysates from PDGF-BB-stimulated RASMCs. Epo-D treatment significantly decreased the level of CDK2 protein, but did not change the levels of CDK4 and cyclin E proteins. Furthermore, Epo-D inhibited the phosphorylation of Rb, a key regulator of the G1 to S phase transition in the cell cycle. These findings suggest that Epo-D may regulate the cell cycle G1-checkpoint proteins as its major molecular mechanism for inhibiting neointimal hyperplasia after in vivo rat carotid artery injury.<<
Could this provide another avenue to market? A long ways off, if so, but this would seem to increase the value of the program.
Cheers, Tuck |
