Curcumin, Demethoxycurcumin, Bisdemothoxycurcumin, Tetrahydrocurcumin, and Turmerones Differentially Regulate Anti-inflammatory and Antiproliferative Responses Through a ROS-Independent Mechanism. [Carcinogenesis] Journal article

Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogues of curcumin (Cur), such as demethoxycurcumin (DMC), bisdemethoxycurcumin (BDMC), tetrahydrocurcumin (THC) and turmerones modulate inflammatory signaling and cell proliferation signaling to same extent as curcumin, was investigated. The results indicate that the relative potency for suppression of TNF-induced NF-kappaB activation was Cur > DMC > BDMC; thus suggesting the critical role of methoxy groups on the phenyl ring. THC, which lacks the conjugated bonds in the central seven-carbon chain, was completely inactive for suppression of the transcription factor. Turmerones also failed to inhibit TNF-induced NF-kappaB activation. The suppression of NF-kappaB activity correlated with inhibition of NF-kappaB reporter activity and with downregulation of COX-2, cyclin D1 and VEGF, all regulated by NF-kappaB. In contrast to NF-kappaB activity, the suppression of proliferation of various tumor cell lines by Cur, DMC, and BDMC, was found to be comparable; indicating the methoxy groups play minimum role in the growth-modulatory effects of curcumin. THC and turmerones were also found to be active in suppression of cell growth but to a much lesser extent than curcumin, DMC and BDMC. Whether suppression of NF-kappaB or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogues of curcumin present in turmeric exhibit variable anti-inflammatory and antiproliferative activities, which do not correlate with their ability to modulate the ROS status.

Carcinogenesis