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Suppression of pro-inflammatory and proliferative pathways by diferuloylmethane (curcumin) and its analogues dibenzoylmethane, dibenzoylpropane, and dibenzylideneacetone: role of Michael acceptors and Michael donors.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2011 Dec 15; Vol. 82 (12), pp. 1901-9. Date of Electronic Publication: 2011 Sep 08. - Publication Year :
- 2011
-
Abstract
- Curcumin, a diferuloylmethane, has been shown to exhibit anti-inflammatory and anti-proliferative activities. Whereas curcumin has both a Michael acceptor and a Michael donor units, its analogues dibenzoylmethane (DBM, a component of licorice) and dibenzoylpropane (DBP) have a Michael donor but not a Michael acceptor unit, and the analogue dibenzylideneacetone (DBA) has a Michael acceptor unit. In the current report, we investigated the potency of DBM, DBP, and DBA in relation to curcumin for their ability to suppress TNF-induced NF-κB activation, NF-κB-regulated gene products, and cell proliferation. We found that all four agents were active in suppressing NF-κB activation; curcumin was most active and DBM was least active. When examined for its ability to inhibit the direct DNA binding activity of p65, a subunit of NF-κB, only DBP inhibited the binding. For inhibition of TNF-induced IKK activation, DBA was most active. For suppression of TNF-induced expression of NF-κB-regulated gene products such as COX-2 (inflammation marker), cyclin D1 (proliferation marker), and VEGF (angiogenesis marker), DBA and curcumin were more active than DBM. Similarly for suppression of proliferation of leukemia (KBM-5), T cell leukemia (Jurkat), prostate (DU145), and breast (MDA-MB-231) cancer cells, curcumin and DBA were most active and DBP was least active. Overall, our results indicate that although curcumin and its analogues exhibit activities to suppress inflammatory pathways and cellular proliferation, a lack of Michael acceptor units in DBM and DBP can reduce their activities.<br /> (Copyright © 2011 Elsevier Inc. All rights reserved.)
- Subjects :
- Angiogenic Proteins genetics
Angiogenic Proteins metabolism
Anti-Inflammatory Agents, Non-Steroidal chemistry
Cell Line, Tumor
Cell Proliferation
Chalcones chemistry
Curcumin analogs & derivatives
Curcumin chemistry
Gene Expression Regulation physiology
Humans
MAP Kinase Kinase Kinases genetics
MAP Kinase Kinase Kinases metabolism
Molecular Structure
Pentanones chemistry
Tumor Necrosis Factor-alpha genetics
Tumor Necrosis Factor-alpha metabolism
Anti-Inflammatory Agents, Non-Steroidal pharmacology
Chalcones pharmacology
Curcumin pharmacology
Pentanones pharmacology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 82
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 21924245
- Full Text :
- https://doi.org/10.1016/j.bcp.2011.09.001