J Dermatol Sci. 2001 Jan;25(1):1-9.
Colchicine and griseofulvin inhibit VCAM-1 expression on human vascular endothelial cells - evidence for the association of VCAM-1 expression with microtubules.

Asahina A, Tada Y, Nakamura K, Tamaki K.

Department of Dermatology, Faculty of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, 113-8655, Tokyo, Japan.

We have previously reported that griseofulvin inhibits VCAM-1 expression on human vascular endothelial cells. Since griseofulvin interferes with microtubule assembly, we used colchicine as another microtubule antagonist and compared it with griseofulvin to further characterize this inhibition. By flow cytometry, colchicine inhibited VCAM-1 induction on TNFalpha-stimulated human dermal microvascular endothelial cells (HDMEC) dose-dependently. Colchicine also inhibited VCAM-1 induction on both TNFalpha- and IL-1alpha-stimulated human umbilical vein endothelial cells (HUVEC). Although this inhibition was reversible, colchicine-treated cells showed slower restoration of its expression than griseofulvin-treated cells. Moreover, co-incubation with a microtubule stabilizer paclitaxel blocked this inhibition, and colchicine-treated cells were more resistant to this blocking than griseofulvin. RT-PCR of HDMEC showed inhibition of the transcript level of VCAM-1 by both antagonists. These results indicate intimate association between VCAM-1 expression and microtubules.


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J Cell Biochem. 2001;81(1):162-71.
Mechanism of colchicine-induced steroidogenesis in rat adrenocortical cells.

Lee LJ, Chen JS, Ko TL, Wang SM.

Department of Anatomy and Cell Biology, College of Medicine, National Taiwan University, 1-1 Jen-Ai Road, Taipei, Taiwan 100.

Conflicting data for the effects of colchicine on cholesterol transport and steroidogenesis raise the question of the role of microtubules in cholesterol transport from the lipid droplet to mitochondria in steroidogenic cells. In this study, using corticosterone radioimmunoassay and immunofluorescence microscopy, we re-evaluated the effects of colchicine on hormone production and morphological changes of lipid droplets' and studied the signaling pathway involved in colchicine-induced steroidogenesis. Colchicine stimulated steroid production in a dose- and time-dependent manner. The structural integrity of both the microtubules and the lipid droplet capsule was destroyed by colchicine treatment. Disruption of the lipid droplet capsule occurred later than microtubule depolymerization. After cessation of colchicine treatment and a 3 h recovery in fresh medium, capsular protein relocated to the droplet surface before the cytoplasmic microtubule network was re-established. beta-lumicolchicine, an inactive analogue of colchicine, disrupted the capsule and increased hormone production without affecting microtubular structure. Thus, microtubule depolymerization is not required for the increase in steroid production and capsular disruption. To explore the signaling pathway involved in colchicine-induced steroidogenesis, we measured intracellular cAMP levels. Unlike ACTH, colchicine did not increase cAMP levels, suggesting that the cAMP-PKA system is not involved. Colchicine and ACTH had additive effects on corticosterone production, whereas colchicine and PMA did not, implying that part of the PKC signaling mechanism may be involved in colchicine-induced steroidogenesis. Cycloheximide, a protein synthesis inhibitor, completely inhibited colchicine-induced steroidogenesis and capsular disruption. These results demonstrate that the steroid production and lipid droplet capsule detachment induced by colchicine are both protein neosynthesis-dependent and microtubule-independent. 2001 Wiley-Liss, Inc.


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J Biol Chem. 1979 Apr 25;254(8):2568-71.
Microtubules and the regulation of 3-hydroxy-3-methylglutaryl coenzyme A reductase.

Volpe JJ.

Cultured C-6 glial cells were utilized to evaluate the effect of antimicrotubular drugs on 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase and cholesterol synthesis. Colchicine, Colcemid, and vinblastine (1.0 muM) caused a marked reduction in HMG-CoA reductase activity and, as a consequence, the rate of cholesterol synthesis in these cells. No effect was observed with lumicolchicine, a mixture of colchicine isomers with no effect on microtubules. The effect of colchicine was apparent within 1 h after addition to the culture medium, and, after 6 h, HMG-CoA reductase activity in treated cells was only approximately 15 to 30% of that in untreated cells. Reductase activity was very sensitive to the concentration of drug added, i.e. cells treated with just 0.1 muM colchicine for 6 h exhibited a 50% lower enzymatic activity than did untreated cells. The lack of a generalized, nonspecific toxic effect on the cells was indicated by the finding of no change in the activities of fatty acid synthetase and NADPH-cytochrome c reductase and the rate of total protein synthesis in cells treated with colchicine (1 muM) for 6 h. A close temporal and quantitative correlation was observed between the effects of colchicine on HMG-CoA reductase and on a parameter of microtubular function, i.e. maintenance of glial cell shape. The data suggest that microtubules are involved in the regulation of HMG-CoA reductase and cholesterol synthesis in C-6 glial cells.


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Eur J Clin Invest. 1979 Apr;9(2 Pt 1):161-6.
Beneficial effects of colchicine in experimental nephrotoxic serum nephritis in the rat.

Penchas S, Charuzi I, Boss JH.

Glomerulonephritis was induced in rats by multiple injections of rabbit anti-rat kidney serum. Colchicine was administered daily for 4 months to nephrotoxic serum treated rats and untreated control animals. Nephritic rats receiving colchicine had significantly less proteinuria and less glomerular damage than unprotected nephritis animals. A possible role for colchicine in the early treatment of human glomerulonephritis is suggested.


Online pharmacy ref source: www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=111949&dopt=Abstract colchicine