The antitumor activities of curcumin and of its isoxazole analogue are not affected by multiple gene expression changes in an MDR model of the MCF-7 breast cancer cell line: Analysis of the possible molecular basis
We examined the effects of curcumin and of its isoxazole analogue MR 39 in the MCF-7 breast cancer cell line and in its multidrug-resistant (MDR) variant MCF-7R. In comparison with MCF-7, MCF-7R lacks estrogen receptor α (ERα) and overexpressess P-glycoprotein (P-gp), different IAPs (inhibitory of apoptosis proteins) and COX-2. Through analyses of the effects on cell proliferation, cycling and death, we have observed that the antitumor activity of curcumin and of the more potent (approximately two-fold) MR 39 is at least equal in the MDR cell line compared to the parental MCF-7. Similar results were observed also in an MDR variant of HL-60 leukemia. RT-PCR evaluations performed in MCF-7 and MCF-7R showed that curcumin or MR 39 produced early modifications in the amounts of relevant gene transcripts, which, however, were mostly diverse (i.e. represented by decreases in IAPs and COX-2 in MCF-7R versus reductions in Bcl-2 and Bcl-XL as well as increases in the Bcl-XS/Bcl-XL ratio in MCF-7) in the two cell lines. These results could not be explained by an involvement of NF-κB (p65 subunit) or STAT3, since the low nuclear levels of these transcription factors present in MCF-7 were only slightly, though significantly, elevated in MCF-7R; moreover, curcumin or MR 39 caused minor changes in NF-κB or STAT3 activation. Overall, these data underline that curcumin or MR 39 antitumor activities are not hampered by P-gp expression or lack of ERα in breast cancer cells. Remarkably, the agents appeared to modify their molecular effects according to the diverse gene expression patterns existing in the MDR and in the parental MCF-7. Clearly, the structure and properties of curcumin can form the basis for the development of antitumor compounds that are more effective against both chemosensitive and MDR cells. .
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Document Type: Research Article
Affiliations: Department of Pharmacological Sciences, University of Palermo, 90127 Palermo, Italy
Publication date: September 1, 2007
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- The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.
The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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