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Curcumin potentiates the antitumor effects of gemcitabine in an orthotopic model of human bladder cancer through suppression of proliferative and angiogenic biomarkers.
- Source :
-
Biochemical pharmacology [Biochem Pharmacol] 2010 Jan 15; Vol. 79 (2), pp. 218-28. Date of Electronic Publication: 2009 Aug 12. - Publication Year :
- 2010
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Abstract
- Little progress has been made in the last three decades in the treatment of bladder cancer. Novel agents that are nontoxic and can improve the current standard of care of this disease are urgently needed. Curcumin, a component of Curcuma longa (also called turmeric), is one such agent that has been shown to suppress pathways linked to oncogenesis, including cell survival, proliferation, invasion and angiogenesis. We investigated whether curcumin has potential to improve the current therapy for bladder cancer, using an orthotopic mouse model. Curcumin potentiated the apoptotic effects of gemcitabine against human bladder cancer 253JBV cells in culture. Electrophoretic mobility shift assay revealed that curcumin also suppressed the gemcitabine-induced activation of the cell survival transcription factor NF-kappaB. In an orthotopic mouse model, bioluminescence imaging revealed that while curcumin alone significantly reduced the bladder tumor volume, maximum reduction was observed when curcumin was used in combination with gemcitabine (P<0.01 versus vehicle; P<0.01 versus gemcitabine alone). Curcumin also significantly decreased the proliferation marker Ki-67 and microvessel density (CD31) (P<0.01 versus vehicle; P<0.01 versus gemcitabine alone), but maximum reduction occurred when it was combined with gemcitabine (P<0.01 versus vehicle; P<0.01 versus gemcitabine alone). Curcumin abolished the constitutive activation of NF-kappaB in the tumor tissue; induced apoptosis, and decreased cyclin D1, VEGF, COX-2, c-myc and Bcl-2 expression in the bladder cancer tissue. Overall our results suggest that curcumin alone exhibits significant antitumor effects against human bladder cancer and it further potentiates the effects of gemictabine, possibly through the modulation of NF-kappaB signaling pathway.
- Subjects :
- Base Sequence
Cell Line, Tumor
DNA Primers
Deoxycytidine pharmacology
Drug Synergism
Humans
Models, Biological
Gemcitabine
Antimetabolites, Antineoplastic pharmacology
Cell Proliferation drug effects
Curcumin pharmacology
Deoxycytidine analogs & derivatives
Neovascularization, Pathologic prevention & control
Urinary Bladder Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1873-2968
- Volume :
- 79
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- Biochemical pharmacology
- Publication Type :
- Academic Journal
- Accession number :
- 19682434
- Full Text :
- https://doi.org/10.1016/j.bcp.2009.08.007