Selective inhibition of cyclooxygenase-2 (COX-2) by 1α,25-dihydroxy-16-ene-23-yne-vitamin D3, a less calcemic vitamin D analog
Article first published online: 17 MAR 2008
Copyright © 2008 Wiley-Liss, Inc.
Journal of Cellular Biochemistry
Volume 104, Issue 5, pages 1832–1842, 1 August 2008
How to Cite
Aparna, R., Subhashini, J., Roy, K. R., Reddy, G. S., Robinson, M., Uskokovic, M. R., Venkateswara Reddy, G. and Reddanna, P. (2008), Selective inhibition of cyclooxygenase-2 (COX-2) by 1α,25-dihydroxy-16-ene-23-yne-vitamin D3, a less calcemic vitamin D analog. J. Cell. Biochem., 104: 1832–1842. doi: 10.1002/jcb.21749
- Issue published online: 19 JUL 2008
- Article first published online: 17 MAR 2008
- Manuscript Accepted: 1 FEB 2008
- Manuscript Received: 11 MAY 2007
- Department of Science and Technology, New Delhi. Grant Numbers: VID & P/11/2001-TT, VII-PRDSF/50/05-06/TDT
- Dabur Research Foundation, Ghaziabad, India
- vitamin D analogs;
Inducible cyclooxygenase-2 (COX-2) has been implicated to play a role in inflammation and carcinogenesis and selective COX-2 inhibitors have been considered as anti-inflammatory and cancer chemopreventive agents. 1α,25-dihydroxyvitamin D3 (1α,25(OH)2D3), the active hormonal form of vitamin D3 also has been considered to be a cancer chemopreventive agent in addition to its important role in maintaining calcium homeostasis. Based on these observations, we studied the direct effect of 1α,25(OH)2D3 and one of its less calcemic synthetic analogs, 1α,25(OH)2-16-ene-23-yne-D3 on the activity of both COX-1 and COX-2 in an in vitro enzyme assay. Preliminary data indicated that both 1α,25(OH)2D3 and 1α,25(OH)2-16-ene-23-yne-D3 inhibited selectively the activity of COX-2 with no effect on the activity of COX-1. Out of the two compounds, 1α,25(OH)2-16-ene-23-yne-D3 was found to be more effective with an IC50 of 5.8 nM. Therefore, the rest of the experiments were performed using 1α,25(OH)2-16-ene-23-yne-D3 only. 1α,25(OH)2-16-ene-23-yne-D3 inhibited the proliferation of lipopolysaccharide (LPS) stimulated mouse macrophage cells (RAW 264.7) with a reduction in the expression of COX-2 along with other inflammatory mediators like inducible nitric oxide synthase (iNOS) and interleukin-2 (IL-2). Furthermore, 1α,25(OH)2-16-ene-23-yne-D3 also inhibited carrageenan induced inflammation in an air pouch of a rat and effectively reduced the expression of COX-2, iNOS, and IL-2 in the tissues of the same air pouch. In both cases, 1α,25(OH)2-16-ene-23-yne-D3 did not show any effect on the expression of COX-1. In summary, our results indicate that 1α,25(OH)2-16-ene-23-yne-D3, a less calcemic vitamin D analog, exhibits potent anti-inflammatory effects and is a selective COX-2 inhibitor. J. Cell. Biochem. 104: 1832–1842, 2008. © 2008 Wiley-Liss, Inc.