Curcumin Based Drug Screening for Inhibitors of NF kappa B in a Cell Model of Prostate Cancer Progression
Final rept. 1 Feb 2007-31 Jan 2008
NEW MEXICO UNIV ALBUQUERQUE SCHOOL OF MEDICINE
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We have identified structurally diverse chemical analogs of the polyphenolic phytochemical Curcumin with an enhanced inhibitory effect against hallmarks of prostate cancer progression. In the androgen independent and bone metastatic cell model of prostate cancer C4-2, these analogs inhibited 1 the activation of the nuclear transcription factor NF kappa B 2 cell proliferation, 3 anchorage independent growth, 4 the expression of Interleukin-6, and 5 the activation of the androgen receptor. In particular, polyphenols with 5-carbon linkers analogs no. 48 and no. 50 and nitrogen side groups analog no. 50 were more efficient than the mother compound Curcumin in inhibiting several hallmarks of prostate cancer progression. The analogs covered in this study display a variety of structural changes, including the length of the carbon chain, the nature of the side groups and the number of the aryl rings. This variety represents a platform for more refined screens of subtle variations of the analogs reported here these screens will be performed in assays specific for the measurement of several molecular markers representing prostate cancer progression and bone metastasis, including the ones reported here and others, such as migration, invasion, adhesion to bone endothelial cells, and mineralization.
- Medicine and Medical Research