Guggulsterone: an inhibitor of nuclear factor - kappaB and IkappaBalpha kinase activation and uses thereof
First Claim
1. A method of inhibiting activation of NF-κ
- B in a cell, comprising the step of contacting the cell with guggulsterone or a guggulsterone analog, wherein guggulsterone or guggulsterone analog suppresses NF-κ
B activation.
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Accused Products
Abstract
The present invention provides an inhibitor of NF-κB, guggulsterone and its analogs. Guggulsterone suppresses NF-κB activation induced by TNF, phorbol ester, okadaic acid, cigarette smoke, H2O2 and IL-1β, as well as constitutive NF-κB activation expressed in most tumor cells. One mechanism by which guggulsterone inhibits activation of NF-κB is through suppression of IκBα phosphorylation and IκBα degradation. NF-κB-dependent gene transcription is modulated by guggulsterone and its analogs. In particular, induction by TNF, TNFR1, TRADD, TRAF2, NIK and IKK, is modulated by guggulsterone and its analogs. In addition, guggulsterone decreased the expression of genes involved in anti-apoptosis (IAP1, XIAP, Bfl-1/A1, bcl-2, cFLIP, survivin), proliferation (cyclin D1, c-myc) and metastasis (MMP-9, COX2 and VEGF).
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Citations
26 Claims
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1. A method of inhibiting activation of NF-κ
- B in a cell, comprising the step of contacting the cell with guggulsterone or a guggulsterone analog, wherein guggulsterone or guggulsterone analog suppresses NF-κ
B activation. - View Dependent Claims (2, 3, 4, 5, 6, 7)
- B in a cell, comprising the step of contacting the cell with guggulsterone or a guggulsterone analog, wherein guggulsterone or guggulsterone analog suppresses NF-κ
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8. A method of downregulating gene expression in a cell, comprising the step of contacting the cell with guggulsterone or a guggulsterone analog, wherein guggulsterone or guggulsterone analog suppresses NF-κ
- B activation and the suppression of NF-κ
B activation down-regulates the expression of anti-apoptotic genes, proliferative genes, metastasis genes, or combinations thereof. - View Dependent Claims (9, 10, 11)
- B activation and the suppression of NF-κ
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12. A method of enhancing the effect of an apoptosis-inducing agent in a cell, comprising the step of contacting the cell with the apoptosis-inducing agent, and guggulsterone or a guggulsterone analog, wherein inhibition of NF-κ
- B activation by guggulsterone results in enhanced apoptosis.
- View Dependent Claims (13, 14)
- 15. A method of treating a cancerous or pre-cancerous state in an individual in need of such treatment, comprising the step of administering a pharmacologically effective dose of guggulsterone to the individual.
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20. A method of increasing cytotoxic effects of a chemotherapeutic agent against cancer in an individual, comprising the step of administering to the individual the chemotherapeutic agent and an inhibitor of the activation of NF-κ
- B, wherein the inhibitor of the activation of NF-κ
B increases the cytotoxic effects of the chemotherapeutic agent against cancer cells in the individual. - View Dependent Claims (21, 23, 24)
- B, wherein the inhibitor of the activation of NF-κ
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25. A method of inhibiting osteoclastogenesis comprising the step of contacting the cell with guggulsterone or a guggulsterone analog, wherein guggulsterone or guggulsterone analog suppresses NF-κ
- B activation and osteoclastogenesis.
- View Dependent Claims (26)
Specification