Carcinogenesis Advance Access originally published online on May 23, 2007
Carcinogenesis 2007 28(8):1765-1773; doi:10.1093/carcin/bgm123
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Curcumin, demethoxycurcumin, bisdemethoxycurcumin, tetrahydrocurcumin and turmerones differentially regulate anti-inflammatory and anti-proliferative responses through a ROS-independent mechanism
Cytokine Research Section, Department of Experimental Therapeutics, Box 143, The University of Texas M. D. Anderson Cancer Center, 1515 Holcombe Boulevard, Houston, TX 77030, USA
1 Division of Food Science and Biotechnology, Graduate School of Agriculture, Kyoto University, Kyoto, 619-0237 Japan
2 Department of Biochemistry, Faculty of Medicine, Chiang Mai University, Chiang Mai 50200, Thailand
3 Sabinsa Corporation, Piscataway, NJ 08854, USA
* To whom correspondence should be addressed. Tel: +1 713 794 1817; Fax: +1 713 794 1613; Email: aggarwal{at}mdanderson.org
Curcumin, a component of turmeric (Curcuma longa), has been shown to exhibit chemopreventive activity. Whether analogs 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 tumor necrosis factor (TNF)-induced nuclear factor-
B (NF-B) 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-B activation. The suppression of NF-B activity correlated with inhibition of NF-B reporter activity and with down-regulation of cyclooxygenase-2, cyclin D1 and vascular endothelial growth factor, all regulated by NF-B. In contrast to NF-B 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-B or cell proliferation, no relationship of any of the curcuminoid was found with reactive oxygen species (ROS) production. Overall, our results demonstrated that different analogs of curcumin present in turmeric exhibit variable anti-inflammatory and anti-proliferative activities, which do not correlate with their ability to modulate the ROS status.
Abbreviations: ar-turmerone, aromatic turmerone; BDMC, bisdemethoxycurcumin; COX-2, cyclooxygenase-2; Cur, pure curcumin; DCF-DA, dichlorodihydrofluorescein diacetate; DMC, demethoxycurcumin; FBS, fetal bovine serum; GSH, glutathione; HPLC, high-performance liquid chromatography; NF-B, nuclear factor-B; ROS, reactive oxygen species; THC, tetrahydrocurcumin; THF, tetrahydrofuran; TLC, thin-layer chromatography; TNF, tumor necrosis factor; VEGF, vascular endothelial growth factor
Received March 20, 2007; revised May 14, 2007; accepted May 14, 2007.
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