Curcumin downregulates cell survival mechanisms in human prostate cancer cell lines

While the role of nuclear transcription factor activator protein-1 (AP-1) i n cell proliferation, and of nuclear factor-kappaB (NF-kappaB) in the suppr ession of apoptosis are known, their role in survival of prostate cancer ce lls is not well understood. We investigated the role of NF-kappaB and AP-1 in the survival of human androgen-independent (DU145) and -dependent (LNCaP ) prostate cancer cell lines. Our results show that the faster rate of prol iferation of DU145 cells when compared to LNCaP cells correlated with the c onstitutive expression of activated NF-kappaB and AP-1 in DU-145 cells. The lack of constitutive expression of NF-kappaB and AP-1 in LNCaP cells also correlated with their sensitivity to the antiproliferative effects of tumor necrosis factor (TNF). TNF induced NF-kappaB activation but not AP-1 activ ation in LNCaP cells. In DU145 cells both c-Fos and c-Jun were expressed an d treatment with TNF activated c-Jun NH2-terminal kinase (JNK), needed for AP-1 activation. In LNCaP cells, however, only low levels of c-Jun was expr essed and treatment with TNF minimally activated JNK. Treatment of cells wi th curcumin, a chemopreventive agent, suppressed both constitutive (DU145) and inducible (LNCaP) NF-kappaB activation, and potentiated TNF-induced apo ptosis. Curcumin alone induced apoptosis in both cell types, which correlat ed with the downregulation of the expression of Bcl-2 and Bcl-xL and the ac tivation of procaspase-3 and procaspase-8. Overall, our results suggest tha t NF-kappaB and AP-1 may play a role in the survival of prostate cancer cel ls, and curcumin abrogates their survival mechanisms.