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Curcumin sensitizes human colorectal cancer to capecitabine by modulation of cyclin D1, COX-2, MMP-9, VEGF and CXCR4 expression in an orthotopic mouse model.
- Source :
-
International journal of cancer [Int J Cancer] 2009 Nov 01; Vol. 125 (9), pp. 2187-97. - Publication Year :
- 2009
-
Abstract
- Because of the poor prognosis and the development of resistance against chemotherapeutic drugs, the current treatment for advanced metastatic colorectal cancer (CRC) is ineffective. Whether curcumin (a component of turmeric) can potentiate the effect of capecitabine against growth and metastasis of CRC was investigated. The effect of curcumin on proliferation of CRC cell lines was examined by mitochondrial dye-uptake assay, apoptosis by esterase staining, nuclear factor-kappaB (NF-kappaB) by electrophoretic mobility shift assay and gene expression by Western blot analysis. The effect of curcumin on the growth and metastasis of CRC was also examined in orthotopically implanted tumors in nude mice. In vitro, curcumin inhibited the proliferation of human CRC cell lines, potentiated capecitabine-induced apoptosis, inhibited NF-kappaB activation and suppressed NF-kappaB-regulated gene products. In nude mice, the combination of curcumin and capecitabine was found to be more effective than either agent alone in reducing tumor volume (p = 0.001 vs. control; p = 0.031 vs. capecitabine alone), Ki-67 proliferation index (p = 0.001 vs. control) and microvessel density marker CD31. The combination treatment was also highly effective in suppressing ascites and distant metastasis to the liver, intestines, lungs, rectum and spleen. This effect was accompanied by suppressed expression of activated NF-kappaB and NF-kappaB-regulated gene products (cyclin D1,c-myc, bcl-2, bcl-xL, cIAP-1, COX-2, ICAM-1, MMP-9, CXCR4 and VEGF). Overall, our results suggest that curcumin sensitizes CRC to the antitumor and antimetastatic effects of capecitabine by suppressing NF-kappaB cell signaling pathway.<br /> ((c) 2009 UICC.)
- Subjects :
- Animals
Apoptosis drug effects
Capecitabine
Cell Line, Tumor
Cell Proliferation drug effects
Colorectal Neoplasms metabolism
Colorectal Neoplasms pathology
Deoxycytidine pharmacology
Drug Synergism
Fluorouracil pharmacology
Humans
Male
Mice
NF-kappa B antagonists & inhibitors
Neoplasm Metastasis prevention & control
Receptors, CXCR4
Antineoplastic Agents pharmacology
Colorectal Neoplasms drug therapy
Curcumin pharmacology
Cyclin D1 genetics
Cyclooxygenase 2 genetics
Deoxycytidine analogs & derivatives
Fluorouracil analogs & derivatives
Gene Expression Regulation, Neoplastic drug effects
Matrix Metalloproteinase 9 genetics
Vascular Endothelial Growth Factor A genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1097-0215
- Volume :
- 125
- Issue :
- 9
- Database :
- MEDLINE
- Journal :
- International journal of cancer
- Publication Type :
- Academic Journal
- Accession number :
- 19623659
- Full Text :
- https://doi.org/10.1002/ijc.24593