Curcumin combined with turmerones, essential oil components of turmeric, abolishes inflammation‐associated mouse colon carcinogenesis

Abstract

Curcumin (CUR), a yellow pigment in turmeric, has marked potential for preventing colon cancer. We recently reported that ar-turmerone (ATM) suppressed nitric oxide (NO) generation in macrophages. In the present study, we explored the molecular mechanisms by which ATM attenuates NO generation and examined the anti-carcinogenesis activity of turmerones (TUR, a mixture of 5 sesquiterpenes including ATM). Both CUR and ATM inhibited lipopolysaccharide (LPS)-induced expression of inducible forms of both nitric oxide synthase and cyclooxygenase (iNOS and COX-2, respectively). A chase experiment using actinomycin D revealed that ATM accelerated the decay of iNOS and COX-2 mRNA, suggesting a post-transcriptional mechanism. ATM prevented LPS-induced translocation of HuR, an AU-rich element-binding protein that determines mRNA stability of certain inflammatory genes. In a colitis model, oral administration of TUR significantly suppressed 2% dextran sulfate sodium (DSS)-induced shortening of the large bowel by 52-58%. We also evaluated the chemopreventive effects of oral feeding of TUR, CUR, and their combinations using a model of dimethylhydradine-initiated and DSS-promoted mouse colon carcinogenesis. At the low dose, TUR markedly suppressed adenoma multiplicity by 73%, while CUR at both doses suppressed adenocarcinoma multiplicity by 63-69%. Interestingly, the combination of CUR and TUR at both low and high doses abolished tumor formation. Collectively, our results led to our hypothesis that TUR is a novel candidate for colon cancer prevention. Furthermore, we consider that its use in combination with CUR may become a powerful method for prevention of inflammation-associated colon carcinogenesis.

Dietary Agents and Phytochemicals in the Prevention and Treatment of Experimental Ulcerative Colitis

“…[122] Turmeric is one of the highly investigated plants and studies have shown it to contain curcuminoids like curcumin [Figure 1], Desmethoxycurcumin, bisdemethoxy curcumin, monodememthoxy curcumin, dihydro curcumin, and cyclocurcumin. [122] Curcumin has been shown to possess potent antioxidant,[123] anti-inflammatory,[124] and cytoprotective effects. [125]…”

Melatonin Enhances the Anti-Tumor Effect of Fisetin by Inhibiting COX-2/iNOS and NF-κB/p300 Signaling Pathways

“…Thus, COX-2 and iNOS represent prime targets for potential treatment of cancer. Some natural products extracted from plants have been studied to be able to selectively inhibit COX-2 and iNOS expression, and have potential to act as anti-cancer molecules [35]–[38]. Both COX-2 and iNOS expression are strictly controlled transcriptionally by the recruitment of transactivators and coactivators, such as NF-κB and p300, to their key promoter regions [39]–[41].…”

Liposomal Formulation of Turmerone-Rich Hexane Fractions fromCurcuma longaEnhances Their Antileishmanial Activity

“…Although there are various reports about curcuminoids as the main molecular targets of Curcuma species, other constituents can be considered unique or coadjuvant molecular target of the curcuminoids in different therapies [24]. The essential oil of turmeric has been pharmacologically studied as an anti-inflammatory, anticancer, and antimicrobial agent among other activities.…”