Colchicine—Update on mechanisms of action and therapeutic uses

Abstract

Objectives To review the literature and provide an updates on the mechanisms of action and therapeutic uses of oral colchicine in arthritis and inflammatory conditions. Methods We performed PubMed database searches through June 2014 for relevant studies in the English literature published since the last update of colchicine in 2008. Searches encompassed colchicine mechanisms of action and clinical applications in medical conditions. A total of 381 articles were reviewed. Results The primary mechanism of action of colchicine is tubulin disruption. This leads to subsequent down regulation of multiple inflammatory pathways and modulation of innate immunity. Newly described mechanisms include various inhibitory effects on macrophages including the inhibition of the NACHT-LRRPYD-containing protein 3 (NALP3) inflammasome, inhibition of pore formation activated by purinergic receptors P2X7 and P2X2, and stimulation of dendritic cell maturation and antigen presentation. Colchicine also has anti-fibrotic activities and various effects on endothelial function. The therapeutic use of colchicine has extended beyond gouty arthritis and Familial Mediterranean Fever, to osteoarthritis, pericarditis and atherosclerosis. Conclusion Further understanding of the mechanisms of action underlying the therapeutic efficacy of colchicine will lead to its potential use in a variety of conditions.

Targeting the Cytoskeleton with Plant-Bioactive Compounds in Cancer Therapy

“…Similar to Vinca alkaloids, colchicine extracted from plants of the genus Colchicum (autumn crocus) is a microtubule-destabilizing agent at high concentrations and stabilizes microtubule dynamics at low concentrations [18]. It irst binds to soluble tubulin, leading to a complex that copolymerizes into the ends of the microtubules and prevents the elongation of the microtubule polymer.…”

The cytoskeleton as a novel target for treatment of renal fibrosis

“…Colchicine, an inhibitor of microtubule polymerization (Leung et al, 2015), decreases RhoA activation in the 5/6 nephrectomy model (Guan et al, 2013). Importantly, colchicine decreased both glomerulosclerosis and interstitial fibrosis, and decreased the upregulation of collagen I, fibronectin and CTGF.…”

Anti-Inflammatory Therapy for Atherosclerosis: Contribution to and Lessons of Rheumatology

“…К противовоспалительным препаратам, используе-мым в ревматологии, относится колхицин, который при-меняется для лечения семейной средиземноморской лихо-радки, болезни Бехчета и подагрического артрита [42]. Один из основных механизмов действия колхицина связан с подавлением синтеза ИЛ1β за счет интерференции с ак-тивацией NALP3-инфламмасомы [43].…”