Project description:Alzheimer's disease (AD) is a chronic neurodegenerative disorder that is associated with the most common type of dementia and is characterized by the presence of deposits of the protein fragment beta‐amyloid (Aβ) in the brain. The natural product mixture of curcuminoids that improves certain defects in innate immune cells of AD patients may selectively enhance Aβ phagocytosis by alteration of gene transcription. In this work, we evaluated the protective effects of curcuminoids in cells from AD patients by investigating the effect of a panel of curcuminoids on NF-kB and BACE1 signaling pathways by gene expression profiling on the clearance of Beta Amyloid (Aβ). Bisdemethoxycurcumin (BDC) showed the most potent protective action to reduce levels of NF‐kB and BACE1, decrease the inflammatory cascade and diminish Aβ aggregates in cells from AD patients. Moreover, mannosylglycoprotein 4-beta-N-acetylglucosaminyltransferase (MGAT3) and vitamin D receptor (VDR) gene mRNAs were up-regulated in peripheral blood mononuclear cells from AD patients treated with BDC. BDC treatment impacts both gene expression, such as Mannosyl (Beta‐1,4‐)‐Glycoprotein Beta‐1,4‐N‐Acetylglucosaminyltransferase, Vitamin D and Toll like receptors and Aβ phagocytosis. Down-regulation of BACE1 and NF-kB following administration suggests a method to treat asymptomatic AD patients with selective curcumins as a dietary supplement.
Project description:Melanoma is the most aggressive form of skin cancer with estimated 48,000 deaths worldwide. The polyphenol curcumin derived from the plant Curcuma longa is well known for its anti-inflammatory and anti-cancerogenic properties. Accordingly, dietary intake of this compound may be suitable for melanoma prevention. However, how this compound affects basic cellular mechanisms in developing melanoma still remains elusive. Therefore, the aim of this study was to investigate for the first time the impact of oral curcumin administration on the miRNA signature of engrafting melanoma. For this purpose, the effects of a 4% curcumin diet on murine B78H1 melanoma were tested in a flank model. Curcumin diet or standard chow (control) was administered two weeks prior to tumor initiation until termination of the experiment. Highly significant chip-based miRNA array analysis was deployed to detect alterations in the miRNA signature of the tumors. Curcumin treatment significantly reduced the growth of the flank tumors. Furthermore the miRNA expression signature in tumors was substantially altered by curcumin intake with mmu-miR-205-5p over 100 times higher expressed when compared to controls. Putative targets of curcumin-induced up-regulated miRNAs were enriched in o-glycan biosynthesis, endoplasmatic reticulum protein processing and different cancer-related pathways. These findings demonstrate a profound alteration of the miRNA expression signature in engrafting curcumin-treated melanoma with mmu-miR-205-5p being up-regulated most significantly. Treatment of male C57BL/6 mice with induced flank tumors (injection of B78H1 cells) either with standard mouse chow (control n=6) or chow enriched with 4% of curcumin (treatment group n=7 )
Project description:Melanoma is the most aggressive form of skin cancer with estimated 48,000 deaths worldwide. The polyphenol curcumin derived from the plant Curcuma longa is well known for its anti-inflammatory and anti-cancerogenic properties. Accordingly, dietary intake of this compound may be suitable for melanoma prevention. However, how this compound affects basic cellular mechanisms in developing melanoma still remains elusive. Therefore, the aim of this study was to investigate for the first time the impact of oral curcumin administration on the miRNA signature of engrafting melanoma. For this purpose, the effects of a 4% curcumin diet on murine B78H1 melanoma were tested in a flank model. Curcumin diet or standard chow (control) was administered two weeks prior to tumor initiation until termination of the experiment. Highly significant chip-based miRNA array analysis was deployed to detect alterations in the miRNA signature of the tumors. Curcumin treatment significantly reduced the growth of the flank tumors. Furthermore the miRNA expression signature in tumors was substantially altered by curcumin intake with mmu-miR-205-5p over 100 times higher expressed when compared to controls. Putative targets of curcumin-induced up-regulated miRNAs were enriched in o-glycan biosynthesis, endoplasmatic reticulum protein processing and different cancer-related pathways. These findings demonstrate a profound alteration of the miRNA expression signature in engrafting curcumin-treated melanoma with mmu-miR-205-5p being up-regulated most significantly.
Project description:Curcumin is a potent modulator of the inflammatory transcriptome in microglia We have performed global gene expression analysis of BV-2 microglial cells under the following conditions: untreated, 20 µM Curcumin-treated, 100ng/ml LPS-treated, or 20 µM Curcumin-treated + 100ng/ml LPS-treated
Project description:Botanicals are widely used as dietary supplements and for the prevention and treatment of disease. Despite a long history of use, there is generally little evidence supporting the efficacy and safety of these preparations. Curcumin has been used to treat a myriad of human diseases and is widely advertised and marketed for its ability to improve health, but there is no clear understanding how curcumin interacts with cells and affects cell physiology. D. discoideum is a simple eukaryotic lead system that allows both tractable genetic and biochemical studies. The studies reported here show novel effects of curcumin on cell proliferation and physiology, and a pleiotropic effect on gene transcription. Transcriptome analysis showed that the effect is two-phased with an early transient effect on the transcription of approximately 5% of the genome, and demonstrates that cells respond to curcumin through a variety of previously unknown molecular pathways. This is followed by later unique transcriptional changes and a protein kinase A dependent decrease in catalase A and three superoxide dismutase enzymes. Although this results in an increase in reactive oxygen species (ROS; superoxide and H2O2), the effects of curcumin on transcription do not appear to be the direct result of oxidation. This study opens the door to future explorations of the effect of curcumin on cell physiology.
Project description:Curcumin, derived from the rhizome of Curcuma longa is a natural anti-cancer agent and has been shown to inhibit proliferation and survival of tumor cells. Although the anti-cancer effects of curcumin are well established, detailed understanding of the signaling pathways altered by curcumin is still unclear. In this study, we carried out SILAC-based quantitative proteomic analysis of CAL 27 cell line, a HNSCC cell line to investigate tyrosine signaling in response to curcumin. Using high resolution Orbitrap Fusion™ Tribrid™ Fourier transform mass spectrometer, we identified 627 phosphotyrosine sites mapping to 357 proteins. We observed alterations in the level of phosphorylation of 307 sites corresponding to 204 proteins upon curcumin treatment.
Project description:Expression analysis was performed with human SUP-T1 cell line infected with HIV alone, treated with curcumin alone and infected with HIV in presence of curcumin. The control untreated sample was compared with all the three types of treatments to calculate the fold change. The purpose of the experiment was to identify set of genes that are dys-regulated during HIV infection and shows normal expression when treated with curcumin. This experiment is useful in identifying the mechanism of anti-HIV activity of curcumin at genetic level.
Project description:miRNA profiling of curcumin treated Y79 cells with untreated Y79 cells (control). Aim of the study to see whether any oncogenes or tumor suppressor genes are regulated on curcumin treatment in Y79 cells.
Project description:Various bioactive food compounds may confer health and longevity benefits, possibly through altering or preserving the human epigenome. While bioactive food compounds are widely being marketed as ‘improving health and longevity’ by counteracting harmful effects of poor nutrition and lifestyle, claimed effects are often not adequately documented. Using the honey bee (Apis mellifera) as a model species, we here employed a multi-step screening approach to investigate seven compounds for effects on lifespan and DNA methylation using ELISA and whole genome bisulfite sequencing (WGBS). A positive longevity effect was detected for valproic acid, isovaleric acid, and cyanocobalamin. For curcumin, we found that lifespan shortening caused by ethanol intake, was restored when curcumin and ethanol were co-administered. Furthermore, we identified region specific DNA methylation changes as a result of ethanol intake. Ethanol specific changes in DNA methylation were fully or partially blocked in honey bees receiving ethanol and curcumin together. Ethanol-affected and curcumin-blocked differentially methylated regions covered genes involved in fertility, temperature regulation and tubulin transport. Our results demonstrate fundamental negative effects of low dose ethanol consumption on lifespan and associated DNA methylation changes and present a proof-of-principle on how longevity and DNA methylation changes can be negated by the bioactive food component curcumin. Our findings provide a fundament for further studies of curcumin in mice and humans and offer an avenue to explore regarding possible prevention of health issues related to alcohol consumption.