Back to Search
Start Over
Curcumin potentiates the antitumor effects of Bacillus Calmette-Guerin against bladder cancer through the downregulation of NF-kappaB and upregulation of TRAIL receptors.
- Source :
-
Cancer research [Cancer Res] 2009 Dec 01; Vol. 69 (23), pp. 8958-66. Date of Electronic Publication: 2009 Nov 10. - Publication Year :
- 2009
-
Abstract
- Although Bacillus Calmette-Guerin (BCG) intravesical therapy is a standard treatment for bladder cancer, eventual failure of response is a major problem. Treatments that can augment BCG therapy are urgently needed. We investigated whether curcumin, a component of Curcuma longa (also called turmeric), has potential to improve the current therapy using in vitro and in vivo MBT-2 murine tumor models. We found that curcumin potentiated BCG-induced apoptosis of human bladder cancer cells. BCG stimulated the release of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) from peripheral mononuclear neutrophils in a dose- and time-dependent manner, whereas curcumin enhanced the upregulation of TRAIL receptors. Electrophoretic mobility shift assay revealed that curcumin also suppressed the BCG-induced activation of the cell survival transcription factor NF-kappaB. In a syngeneic bladder cancer model, curcumin alone reduced the bladder tumor volume, but a significantly greater reduction was observed when BCG and curcumin were used in combination (P < 0.0001 versus control; P < 0.003 versus BCG alone). This was accompanied by a significant decrease in the proliferation marker Ki-67 (P < 0.01 versus control; P < 0.01 versus BCG alone) and microvessel density (CD31; P < 0.01 versus control; P < 0.01 versus BCG alone), decreased NF-kappaB in tumor tissue compared with the control, induced apoptosis, and decreased cyclin D1, vascular endothelial growth factor, cyclooxygenase-2, c-myc, and Bcl-2 expression in the tumor tissue. Upregulation of TRAIL receptor by the combination was also observed in tumor tissues. Overall, our results suggest that curcumin potentiates the antitumor effect of BCG through the inhibition of NF-kappaB and induction of TRAIL receptors in bladder cancer cells.
- Subjects :
- Animals
Antineoplastic Combined Chemotherapy Protocols pharmacology
Apoptosis drug effects
Cell Growth Processes drug effects
Cell Line, Tumor
Cyclooxygenase 2 biosynthesis
Down-Regulation drug effects
Drug Synergism
Female
Humans
Mice
Mice, Inbred C3H
Neovascularization, Pathologic drug therapy
Neovascularization, Pathologic pathology
TNF-Related Apoptosis-Inducing Ligand biosynthesis
Up-Regulation drug effects
Urinary Bladder Neoplasms blood supply
Urinary Bladder Neoplasms metabolism
Urinary Bladder Neoplasms pathology
Vascular Endothelial Growth Factor A biosynthesis
BCG Vaccine pharmacology
Curcumin pharmacology
NF-kappa B biosynthesis
Receptors, TNF-Related Apoptosis-Inducing Ligand biosynthesis
Urinary Bladder Neoplasms therapy
Subjects
Details
- Language :
- English
- ISSN :
- 1538-7445
- Volume :
- 69
- Issue :
- 23
- Database :
- MEDLINE
- Journal :
- Cancer research
- Publication Type :
- Academic Journal
- Accession number :
- 19903839
- Full Text :
- https://doi.org/10.1158/0008-5472.CAN-09-2045