Research article summary (published 30 Oct 2009):

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.

Full 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. (c) 2009 UICC.

Author information

Author/s: Kunnumakkara, Ajaikumar B (AB); Diagaradjane, Parmeswaran (P); Anand, Preetha (P); Kuzhuvelil, Harikumar B (HB); Deorukhkar, Amit (A); Gelovani, Juri (J); Guha, Sushovan (S); Krishnan, Sunil (S); Aggarwal, Bharat B (BB);

Affiliation: Department of Experimental Therapeutics, The University of Texas M. D. Anderson Cancer Center, Houston, TX 77030, USA.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: International journal of cancer. Journal international du cancer (Int J Cancer), published in United States. (Language: eng)

Reference: 2009-Nov; vol 125 (issue 9) : pp 2187-97

Dates: Created 2009/09/03; Completed 2009/09/15;

PMID: 19623659, status: MEDLINE (last retrieval date: 9/15/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

External Links for this article
(including full text providers, if available):

Click Electronic Full-text Provider Links to see options for finding the electronic full text links to this article. Note there may be a subscription or fee required for access to the full text. See our FAQ for information on finding FREE full text articles.

This article may also be located in paper journal collections available in many libraries. Use the Journal and Publication Information above to find the full article.

MeSH headings (categories)

This article was linked to the MESH Headings shown below.

Animals Antineoplastic Agents - pharmacology Apoptosis - drug effects Cell Line, Tumor Cell Proliferation - drug effects Colorectal Neoplasms - drug therapy; metabolism; pathology Curcumin - pharmacology Cyclin D1 - genetics Cyclooxygenase 2 - genetics Deoxycytidine - analogs & derivatives; pharmacology Drug Synergism

Drug Synergism Fluorouracil - analogs & derivatives; pharmacology Gene Expression Regulation, Neoplastic - drug effects Humans Male Matrix Metalloproteinase 9 - genetics Mice NF-kappa B - antagonists & inhibitors Neoplasm Metastasis - prevention & control Receptors, CXCR4 Vascular Endothelial Growth Factor A - genetics

Associated Chemicals: Antineoplastic Agents (0) ; CXCR4 protein, human (0) ; NF-kappa B (0) ; Receptors, CXCR4 (0) ; Vascular Endothelial Growth Factor A (0) ; Cyclin D1 (136601-57-5) ; capecitabine (154361-50-9) ; Curcumin (458-37-7) ; Fluorouracil (51-21-8) ; Deoxycytidine (951-77-9) ; Cyclooxygenase 2 (EC 1.14.99.1) ; PTGS2 protein, human (EC 1.14.99.1) ; Matrix Metalloproteinase 9 (EC 3.4.24.35)

Related articles

These are the highest related articles currently in the database:

• Curcumin potentiates antitumor activity of gemcitabine in an orthotopic model of pancreatic cancer through suppression of proliferation, angiogenesis, and inhibition of nuclear factor-kappaB-regulated gene products. 13 Apr 2007
• Curcumin enhances the effects of 5-fluorouracil and oxaliplatin in mediating growth inhibition of colon cancer cells by modulating EGFR and IGF-1R. 13 Jan 2008
• DPD is a molecular determinant of capecitabine efficacy in colorectal cancer. 30 Jul 2007
• Curcumin induces cell-arrest and apoptosis in association with the inhibition of constitutively active NF-kappaB and STAT3 pathways in Hodgkin's lymphoma cells. 29 Jun 2008
• [Curcumin inhibits the expression of vascular endothelial growth factor and androgen-independent prostate cancer cell line PC-3 in vitro] 30 Jan 2008
• [Up-regulates the expression of maspin gene in prostate cancer cell line LNCaP] 29 Nov 2006
• Neurological complications of cancer chemotherapy. 29 Jun 2006
• Effects of capecitabine and vinorelbine on cell proliferation, metabolism and COX2 and p16 expression in breast cancer cell lines and solid tumour tissues. 12 Sep 2007
• Transmission of apoptosis in human colorectal tumor cells exposed to capecitabine, Xeloda, is mediated via Fas. 30 Aug 2002
• Capecitabine: preclinical pharmacology studies. 30 Oct 2000

See 100+ related articles.

Related Article Map

Legend: - FREE Full text Article. - Abstract only. - Title only. More help.

See a large map of 100+ related articles.