Treatment of human multiple myeloma by curcumin

Details Treatment of human multiple myeloma by curcumin Treatment of human multiple myeloma by curcumin

A - Human Necessities

61

K

A61K 31/12 (2006.01) A61K 31/175 (2006.01) A61K 31/195 (2006.01) A61K 31/44 (2006.01) A61K 31/573 (2006.01) A61K 31/66 (2006.01) A61K 36/9066 (2006.01) A61P 35/00 (2006.01)

Patent

CA 2489947

All multiple myeloma cell lines examined showed constitutively active IkB kinase (IKK), IkB.alpha. phosphorylation and constitutively active NF-kB. Curcumin, a chemopreventive agent, suppressed constitutive IkB.alpha. phosphorylation through inhibition of IKK activity and downregulated NF-kB. Curcumin also downregulated expression of NF-kB-regulated gene products such as IkB.alpha., Bcl-2, Bcl-xL, cyclin D1 and interleukin-6. Consequently, curcumin suppressed multiple myelona cell proliferation and arrested cells at the G1/S phase of the cell cycle. Curcumin also induced apoptosis and chemosensitivity to vincristine. Overall, results presented herein provide a molecular basis for the treatment of multiple myelona patients with this pharmacologically safe agent.

Toutes les lignées cellulaires de myélome multiple qui ont été examinées présentent une kinase I.kappa.B (IKK) constitutivement active, une phosphorylation d'I.kappa.B.alpha. et une NF-.kappa.B constitutivement active. La curcumine, un agent chimiopréventif, permet de supprimer la phosphorylation d'I.kappa.B.alpha. constitutive en inhibant l'activité d'IKK et en régulant négativement NF-.kappa.B. La curcumine régule aussi négativement l'expression de produits géniques régulés par NF-.kappa.B tels que I.kappa.B.alpha., Bcl-2, Bcl-x<SB>L</SB>, la cycline D1 et l'interleukine 6. Par conséquent, la curcumine permet de supprimer la prolifération de cellules de myélome multiple et d'arrêter les cellules à la phase G1/S du cycle cellulaire. La curcumine induit également l'apoptose et une chimiosensibilité à la vincristine. De manière générale, les résultats présentés fournissent une base moléculaire pour traiter des patients atteints de myélome multiple à l'aide de cet agent pharmacologiquement sûr.

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