Anticancer potential of curcumin - Norma Jones Houston Myeloma

52 Pages·2003·0.36 MB·English

by  Bharat Aggarwal

Anticancer potential of
curcumin
Bharat B. Aggarwal, Ph.D.
Cytokine Research Section,
Department of Bioimmunotherapy,
The University of Texas M.D. Anderson Cancer Center,
Houston, Texas, U.S.A.

Source of Curcumin
Turmeric
(Curcuma longa)
Structure of curcumin
O O
CH3O
OCH3
Curcumin I
(77%)
HO OH
O O
Curcumin II
OCH3
Demethoxycurcumin
(17%)
HO OH
O O
Curcumin III
Bis-Demethoxycurcumin
(3%; less active)
HO OH
Different stages of cancer progression and
its suppression by curcumin
Constitutive activation of Overexpression of Overexpression of
transcription factors (cid:190)Oncogenes (cid:190)Matrix metalloproteases
(cid:190)HER2 (cid:190)Cyclooxygenase-2
(cid:190)AP-1& NF-κB
(cid:190)Growth factors (cid:190)Adhesion molecules
(e.g; EGF, PDGF, FGF) (cid:190)Chemokine
(cid:190)Tumor Suppressor genes (cid:190)Growth factor receptors (cid:190)TNF
(cid:190)Survival factors
(e.g; Survivin,Bcl-2 and Bcl-xl)
(cid:190)Cyclin D1
(cid:190)Decoy receptor
Transformation Proliferation Invasion
Normal Tumor Tumor Tumor
cells cells growth Metastasis
curcumin
Activation of transcription factor
Nuclear Factor-kappa B is
suppressed by curcumin
Singh S, and Aggarwal BB.
J Biol Chem. 1995 Oct 20;270 (42):24995-5000.
Role of NF-κB in Development of Cancer
Anti-apoptosis/survival
Tumor promotion
e.g; bcl-xl, cIAP, survivin, cFLIP,
e.g; COX2, iNOS, MMP-9, uPA
TRAF, SOD, γ-GCS
Inflammation Proliferation
NF-κB
TNF, IL-1, Chemokines e.g; TNF, IL-1, IL-6
Angiogenesis
VEGF, TNF, IL-1, IL-8
Metastasis
e.g; ICAM-1, VCAM-1, ELAM-1
Curcumin inhibits constitutive NF-
κB, IκBα kinase, inhibits
proliferation, and induces apoptosis
in human multiple myeloma cells
Bharti A., Donato N., Singh S., Aggarwal B.B.
BLOOD, 101, 2003, 1053-1062
Curcumin Inhibits Constitutive
and Interleukin-6-Inducible
STAT3 Phosphorylation in
Human Multiple Myeloma Cells
Alok C. Bharti, Nicholas Donato, and
Bharat B. Aggarwal
Journal of Immunology, in press)
(
Nuclear Factor-κB and STAT3
are Constitutively Active in
CD138+ Cells Derived from
Multiple Myeloma Patients and
Their Suppression Leads to
Apoptosis
Alok C. Bharti, James M. Reuben, Donna Weber,
Raymond Alexanian, Moshe Talpaz and
Bharat B. Aggarwal
(submitted)