Scope: There is extensive pre-clinical evidence for utility of curcuminoids across many diseases with a particular focus on cancer prevention, yet there remains a paucity of clinical evidence for its approved use. To assess current knowledge on the broader potential for clinical efficacy of curcumin and in particular, in cancer prevention strategies, this study undertook a systematic review determining the number and quality of randomized controlled trials (RCTs) undertaken across any pathology. Methods and Results: Search strategies for RCTs using a quantifiable amount of curcuminoids, are applied across Medline (Medical Literature Analysis and Retrieval System Online), Embase (Excerpta Medica dataBASE), Cochrane and clinicaltrials.gov. There are 314 curcuminoid-based RCTs, with 100 of these revealing significant within-and between-group changes relating to the primary outcome. Twenty three studies are conducted in a setting where there is an increased risk of cancer. Fifteen of these meet all prescribed quality criteria, and 10 reveal positive outcomes. Conclusions: A substantial number of studies reveal positive outcomes following curcumin use. However, despite the vast array of preclinical data, there are relatively few RCTs conducted in the prevention setting. Future approaches to trials must deliver improved robustness and credibility of curcumin-related research to facilitate approvals for use in clinical settings.
Background: The transcription factor Nanog is crucial for the self-renewal of cancer stem-like cells (CSCs). Nanog expression in colorectal cancer (CRC) tissue correlates with lymph node metastasis and poor prognosis. Since Nanog is not expressed in most tissues, including normal adult stem-cells, it represents a therapeutic target specific to cancer cells. Curcumin inhibits proliferation and expansion of CSCs derived from CRC and adenomas. In NOD/SCID mice bearing xenografts from patient-derived CRC CSCs, curcumin significantly inhibited tumour growth and improved survival. In addition, curcumin binds directly to Nanog recombinant protein (quantified using microscale thermophoresis). We have developed 3D in-vitro primary human explant models to further characterise the effects of curcumin on Nanog. In this work the hypothesis is tested that Nanog may be an early marker of response for CRC prevention agents. Methods: Patient-derived CRC and adenoma tissue was cubed (2x2x2mm) and treated for 24 hours with curcumin. Following treatment, explant tissues were processed for analysis by immunohistochemistry (IHC) (n=6) and flow cytometry (n=17). The effect of curcumin on CSCs (defined by expression of aldehyde dehydrogenase (ALDH) or Nanog) and differentiation (via Mucin 2 expression) was analysed using IHC. Additionally, cells expressing Nanog (Nanog+) or Nanog plus proliferation marker Ki67 (Nanog+Ki67+) were assessed using flow cytometry. Results: A range of adenoma (n=5) and Dukes stage A-C CRC (n=18) samples were studied. Following exposure to curcumin, a 30% reduction was observed in Nanog+ and Nanog+Ki67+ cells. Nanog+ cell number was decreased in a curcumin concentration-dependent fashion in 6 samples and concentration-independently in a further 8. No response was observed in 3 samples. A reduction in Nanog and ALDH with concurrent increase in differentiation was observed via IHC in one sample. Conclusion: Our data suggest Nanog is targeted by curcumin in adenoma and CRC tissues. Nanog may serve as a biomarker in clinical trials to identify individuals most amenable to treatment with curcumin alone or in combination treatment. Crucially, this will help select those who are likely to benefit from curcumin as a cancer prevention agent. Ultimately, this concept may be applicable to the evaluation of novel CRC prevention agents. Citation Format: Sam Khan, Ankur Karmokar, Zahirah Sidat, Nalini Foreman, David Moore, Jennifer Higgins, Emma Parrott, Despoina Theofanous, Dominic Hobbs, Lynne Howells, Anne Thomas, Karen Brown. Targeting Nanog in 3D explant models for the evaluation of cancer prevention agents [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 258.
The polyphenol resveratrol, widely known for its cancer protective activities has been shown to protect against the pro-tumorigenic effects induced by high-fat diets (HFD) in mouse models of colorectal cancer (CRC). Although, the mechanisms of actions of this compound in humans still remain elusive, recent studies suggest its effects may be mediated partly through its interaction with the gut microbiota. Here we sought to determine the changes induced by HFD on the intestinal microbiome and the impact of resveratrol supplementation on these alterations in a mouse model of BRAFV600E mutant CRC. BRAFV600E; BRAFWT (wild-type) mice were randomised into 8 groups and fed either a standard diet or HFD supplemented with low or high-dose of resveratrol (0.7mg/kg/day and 14mg/kg/day, respectively) for 6-weeks. The mouse faecal microbial profile was then assessed by targeting the V3-V4 area of the bacterial 16S rRNA gene. Consumption of HFD was associated with significant alternations in the gut microbiome composition in both BRAFV600E and BRAFWT based on beta-diversity analysis (PADONIS<0.05). HFD increased the Firmicutes and Clostridia abundance in BRAFWT compared to animals on a standard diet (P<0.01, P<0.008 respectively), while in BRAFV600E mice, alterations were observed in lower taxonomic levels including the enrichment of Faecalibaculum (P<0.02) and growth inhibition of Lactobacillus johnsonhii (P<0.05). High-dose resveratrol resulted in significant differences in the microbial composition compared to HFD-treated group in the BRAFV600E mice (PADONIS<0.05) but not in BRAFWT . Resveratrol administration did not counteract the HF-induced taxonomic changes but high-dose resveratrol changed Muribaculum, and UBA181 genera abundances in BRAFV600E mice (P<0.001 and P<0.05 respectively) compared to HF-treated mice. Low dose resveratrol had no significant effects on bacterial abundance in both BRAFV600E and BRAFWT mice. It was also observed that BRAFV600E mutation influenced the gut microbiome independently of diet based on beta and alpha-diversity (PADONIS<0.05, PChao1<0.05 respectively). Resveratrol administration modified the gut microbiota composition of BRAFV600E mice but did not completely reverse the HFD-induced changes indicating that alternative mechanisms may contribute to the protective effects of resveratrol in this mouse model. Citation Format: Despoina Theofanous, Hong Cai, Karen Brown. Exploring the effects of resveratrol on the gut microbiome in high fat diet-fed BRAFV600E mutant mice [abstract]. In: Proceedings of the Second Biennial NCI Meeting: Translational Advances in Cancer Prevention Agent Development (TACPAD); 2022 Sep 7-9. Philadelphia (PA): AACR; Can Prev Res 2022;15(12 Suppl_2): Abstract nr A020.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
hi@scite.ai
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.