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dc.contributor.authorShakibaei, M.*
dc.contributor.authorMobasheri, A.*
dc.contributor.authorLueders, C.*
dc.contributor.authorBusch, F.*
dc.contributor.authorShayan, P.*
dc.contributor.authorGoel, A.*
dc.date.accessioned2014-04-28T11:20:03Z
dc.date.available2014-04-28T11:20:03Z
dc.date.issued2013
dc.identifier.citationShakibaei, M., Mobasheri, A., Lueders, C., Busch, F., Shayan, P., Goel, A. (2013) Curcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-kappaB and Src protein kinase signaling pathways. PLoS One, 8 (2), e57218.
dc.identifier.urihttp://hdl.handle.net/10454/6183
dc.description.abstractOBJECTIVE: Development of treatment resistance and adverse toxicity associated with classical chemotherapeutic agents highlights the need for safer and effective therapeutic approaches. Herein, we examined the effectiveness of a combination treatment regimen of 5-fluorouracil (5-FU) and curcumin in colorectal cancer (CRC) cells. METHODS: Wild type HCT116 cells and HCT116+ch3 cells (complemented with chromosome 3) were treated with curcumin and 5-FU in a time- and dose-dependent manner and evaluated by cell proliferation assays, DAPI staining, transmission electron microscopy, cell cycle analysis and immunoblotting for key signaling proteins. RESULTS: The individual IC50 of curcumin and 5-FU were approximately 20 microM and 5 microM in HCT116 cells and 5 microM and 1 microM in HCT116+ch3 cells, respectively (p<0.05). Pretreatment with curcumin significantly reduced survival in both cells; HCT116+ch3 cells were considerably more sensitive to treatment with curcumin and/or 5-FU than wild-type HCT116 cells. The IC50 values for combination treatment were approximately 5 microM and 1 microM in HCT116 and 5 microM and 0.1 microM in HCT116+ch3, respectively (p<0.05). Curcumin induced apoptosis in both cells by inducing mitochondrial degeneration and cytochrome c release. Cell cycle analysis revealed that the anti-proliferative effect of curcumin and/or 5-FU was preceded by accumulation of CRC cells in the S cell cycle phase and induction of apoptosis. Curcumin potentiated 5-FU-induced expression or cleavage of pro-apoptotic proteins (caspase-8, -9, -3, PARP and Bax), and down-regulated anti-apoptotic (Bcl-xL) and proliferative (cyclin D1) proteins. Although 5-FU activated NF-kappaB/PI-3K/Src pathway in CRC cells, this was down-regulated by curcumin treatment through inhibition of IkappaBalpha kinase activation and IkappaBalpha phosphorylation. CONCLUSIONS: Combining curcumin with conventional chemotherapeutic agents such as 5-FU could provide more effective treatment strategies against chemoresistant colon cancer cells. The mechanisms involved may be mediated via NF-kappaB/PI-3K/Src pathways and NF-kappaB regulated gene products.
dc.relation.isreferencedbyhttp://dx.doi.org/10.1371/journal.pone.0057218
dc.subjectAntineoplastic agents; Therapeutic use;
dc.subjectApoptosis; Drug effects;
dc.subjectBlotting; Western;
dc.subjectCell line; Tumor;
dc.subjectColorectal neoplasms; Drug therapy; Enzymology; Metabolism; Pathology;
dc.subjectCurcumin; Pharmacology;
dc.subjectDrug synergism;
dc.subjectFluorouracil;
dc.subjectHumans;
dc.subjectMicroscopy; Electron; Transmission;
dc.subjectNF-kappa B; Antagonists & inhibitors;
dc.subjectSignal transduction;
dc.subjectsrc-Family Kinases;
dc.subjectREF 2014
dc.titleCurcumin enhances the effect of chemotherapy against colorectal cancer cells by inhibition of NF-kappaB and Src protein kinase signaling pathways
dc.typeArticle


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