Potent growth suppressive activity of curcumin in human breast cancer cells: Modulation of Wnt/beta-catenin signaling.
Abnormal activation of the Wnt/beta-catenin signaling pathway and subsequent upregulation of beta-catenin driven downstream targets-c-Myc and cyclin D1 is associated with development of breast cancer. The objective of our study was to determine if curcumin could modulate the key elements of Wnt pathway in breast cancer cells; an effect that might underscore its usefulness for chemoprevention/treatment of this malignancy. Curcumin showed a cytotoxic effect on MCF-7 cells with 50% inhibitory concentration (IC(50)) of 35microM; while IC(50) for MDA-MB-231 cells was 30microM. Treatment with low cytostatic dose of 20microM curcumin showed G(2)/M arrest in both breast cancer cells. The effect of curcumin (20microM) treatment on expression of Wnt/beta-catenin pathway components in breast cancer cells (MCF-7 and MDA-MB-231) was analyzed by immunofluorescence and Western blotting. Curcumin was found to effectively inhibit the expression of several Wnt/beta-catenin pathway components-disheveled, beta-catenin, cyclin D1 and slug in both MCF-7 and MDA-MB-231. Immunofluorescence analysis showed that curcumin markedly reduced the nuclear expression of disheveled and beta-catenin proteins. Further, the protein levels of the positively regulated beta-catenin targets-cyclin D1 and slug, were downregulated by curcumin treatment. The expression levels of two integral proteins of Wnt signaling, GSK3beta and E-cadherin were also altered by curcumin treatment. In conclusion, our data demonstrated that the efficacy of curcumin in inhibition of cell proliferation and induction of apoptosis might occur through modulation of beta-catenin pathway in human breast cancer cells.
Prasad
Chandra P
CP
Department of Anatomy, Vardhman Mahavir Medical College and Safdarjung Hospital, Ansari Nagar, New Delhi, India.
Rath
Gayatri
G
Mathur
Sandeep
S
Bhatnagar
Dinesh
D
Ralhan
Ranju
R
D015153:Blotting, Western; D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D002453:Cell Cycle / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects*; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000378:metabolism*; D051176:beta Catenin / Q000378:metabolism*
D051153:Wnt Proteins; D051176:beta Catenin; D003474:Curcumin