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      Promising anti-tumor properties of bisdemethoxycurcumin: A naturally occurring curcumin analogue

      , ,
      Journal of Cellular Physiology
      Wiley-Blackwell

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          Abstract

          Curcuminoids are turmeric-extracted phytochemicals with documented chemopreventive and anti-tumor activities against several types of malignancies. Curcuminoids can modulate several molecular pathways and cellular targets involved in different stages of tumor initiation, growth, and metastasis. Bisdemethoxycurcumin (BDMC) is a minor constituent (approximately 3%) of curcuminoids that has been shown to be more stable than the other two main curcuminoids, that is, curcumin and demthoxycurcumin. Recent studies have revealed that BDMC has anti-tumor effects exerted through a multimechanistic mode of action involving inhibition of cell proliferation, invasion and migration, metastasis and tumour growth, and induction of apoptotic death in cancer cells. The present review discusses the findings on the anti-tumor effects of BDMC, underlying mechanisms, and the relevance of finding for translational studies in human.

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          Most cited references68

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          Curcumin Extract for Prevention of Type 2 Diabetes

          OBJECTIVE To assess the efficacy of curcumin in delaying development of type 2 diabetes mellitus (T2DM) in the prediabetic population. RESEARCH DESIGN AND METHODS This randomized, double-blinded, placebo- controlled trial included subjects (n = 240) with criteria of prediabetes. All subjects were randomly assigned to receive either curcumin or placebo capsules for 9 months. To assess the T2DM progression after curcumin treatments and to determine the number of subjects progressing to T2DM, changes in β-cell functions (homeostasis model assessment [HOMA]-β, C-peptide, and proinsulin/insulin), insulin resistance (HOMA-IR), anti-inflammatory cytokine (adiponectin), and other parameters were monitored at the baseline and at 3-, 6-, and 9-month visits during the course of intervention. RESULTS After 9 months of treatment, 16.4% of subjects in the placebo group were diagnosed with T2DM, whereas none were diagnosed with T2DM in the curcumin-treated group. In addition, the curcumin-treated group showed a better overall function of β-cells, with higher HOMA-β (61.58 vs. 48.72; P < 0.01) and lower C-peptide (1.7 vs. 2.17; P < 0.05). The curcumin-treated group showed a lower level of HOMA-IR (3.22 vs. 4.04; P < 0.001) and higher adiponectin (22.46 vs. 18.45; P < 0.05) when compared with the placebo group. CONCLUSIONS A 9-month curcumin intervention in a prediabetic population significantly lowered the number of prediabetic individuals who eventually developed T2DM. In addition, the curcumin treatment appeared to improve overall function of β-cells, with very minor adverse effects. Therefore, this study demonstrated that the curcumin intervention in a prediabetic population may be beneficial.
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            Mitochondrial Dysfunction in Cancer

            A mechanistic understanding of how mitochondrial dysfunction contributes to cell growth and tumorigenesis is emerging beyond Warburg as an area of research that is under-explored in terms of its significance for clinical management of cancer. Work discussed in this review focuses less on the Warburg effect and more on mitochondria and how dysfunctional mitochondria modulate cell cycle, gene expression, metabolism, cell viability, and other established aspects of cell growth and stress responses. There is increasing evidence that key oncogenes and tumor suppressors modulate mitochondrial dynamics through important signaling pathways and that mitochondrial mass and function vary between tumors and individuals but the significance of these events for cancer are not fully appreciated. We explore the interplay between key molecules involved in mitochondrial fission and fusion and in apoptosis, as well as in mitophagy, biogenesis, and spatial dynamics of mitochondria and consider how these distinct mechanisms are coordinated in response to physiological stresses such as hypoxia and nutrient deprivation. Importantly, we examine how deregulation of these processes in cancer has knock on effects for cell proliferation and growth. We define major forms of mitochondrial dysfunction and address the extent to which the functional consequences of such dysfunction can be determined and exploited for cancer diagnosis and treatment.
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              Physical and Chemical Stability of Curcumin in Aqueous Solutions and Emulsions: Impact of pH, Temperature, and Molecular Environment.

              The utilization of curcumin as a nutraceutical in food and supplement products is often limited because of its low water solubility, poor chemical stability, and low oral bioavailability. This study examined the impact of pH, storage temperature, and molecular environment on the physical and chemical stability of pure curcumin in aqueous solutions and in oil-in-water emulsions. Unlike naturally occurring curcuminoid mixtures (that contain curcumin, demethoxy-curcumin, and bisdemethoxy-curcumin), pure curcumin was highly unstable to chemical degradation in alkaline aqueous solutions (pH ≥7.0) and tended to crystallize out of aqueous acidic solutions (pH 85% of curcumin was retained by emulsions stored under acidic conditions (pH <7), whereas 62, 60, and 53% was retained by emulsions stored at pH 7.0, 7.4, and 8.0, respectively. There was little change in the color of curcumin-loaded emulsions when stored under acidic conditions, but their yellow color faded when stored under alkaline conditions. There was no evidence of droplet aggregation or creaming in emulsions stored for 31 days at ambient temperature. These results suggest that emulsion-based delivery systems may be suitable for improving the water dispersibility and chemical stability of curcumin, which would facilitate its application in foods and supplements.
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                Author and article information

                Journal
                Journal of Cellular Physiology
                J Cell Physiol
                Wiley-Blackwell
                00219541
                February 2018
                February 16 2018
                : 233
                : 2
                : 880-887
                Article
                10.1002/jcp.25795
                28075008
                98fabe14-7d1c-4c12-92e6-b2780140a3ef
                © 2018

                http://doi.wiley.com/10.1002/tdm_license_1.1

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