Mechanistic insights into anti-cancer properties of oligomeric proanthocyanidins from grape seeds in colorectal cancer
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ABSTRACT:
PROVIDER: PRJNA431467 | ENA |
REPOSITORIES: ENA
Dataset's files
| Action | DRS | |||
|---|---|---|---|---|
| SRR6509700.fastq.gz | Fastqsanger.gz | |||
| SRR6509710.fastq.gz | Fastqsanger.gz | |||
| SRR6509720.fastq.gz | Fastqsanger.gz | |||
| SRR6509701.fastq.gz | Fastqsanger.gz | |||
| SRR6509711.fastq.gz | Fastqsanger.gz |
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Project description:Although the anti-cancer properties of Oligomeric Proanthocyanidins (OPCs) from grape seeds has been well recognized, the molecular mechanisms by which they exert anti-cancer effects are poorly understood. In this study, through comprehensive RNA-sequencing based gene-expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affects several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs was significantly more potent at decreasing xenograft tumor growth compared to the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared to GSE. Further, we validated alteration of cell cycle and DNA replication associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exerts anti-cancer properties in colorectal cancer.
2018-02-28 | GSE109607 | GEO
Project description:Although the anticancer properties of oligomeric proanthocyanidins (OPCs) from grape seeds have been well recognized, the molecular mechanisms by which they exert anticancer effects are poorly understood. In this study, through comprehensive RNA-sequencing-based gene expression profiling in multiple colorectal cancer cell lines, we for the first time illuminate the genome-wide effects of OPCs from grape seeds in colorectal cancer. Our data revealed that OPCs affect several key cancer-associated genes. In particular, genes involved in cell cycle and DNA replication were most significantly and consistently altered by OPCs across multiple cell lines. Intriguingly, our in vivo experiments showed that OPCs were significantly more potent at decreasing xenograft tumor growth compared with the unfractionated grape seed extract (GSE) that includes the larger polymers of proanthocyanidins. These findings were further confirmed in colorectal cancer patient-derived organoids, wherein OPCs more potently inhibited the formation of organoids compared with GSE. Furthermore, we validated alteration of cell cycle and DNA replication-associated genes in cancer cell lines, mice xenografts as well as patient-derived organoids. Overall, this study provides an unbiased and comprehensive look at the mechanisms by which OPCs exert anticancer properties in colorectal cancer.
| S-EPMC5972632 | biostudies-literature
Project description:Grape Proanthocyanidins Modulate MicroRNA Expression in Human pancreatic cancer cells
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Project description:Mi(cro)RNAs are small non-coding RNAs of 18-25 nucleotides in length that modulate gene expression at the posttranscriptional level. Grape seed proanthocyanidins (GSPs), a biologically active component of grape seeds, have been shown to have positive effects on anti-cancer. In current study, to explore whether GSPs can regulate miRNA expression and possible molecular mechanisms involved in anti-cancer, we prepared the pancreatic cancer (PC) cells samples (SS3, SS12 and SS24) at 3, 12 and 24h after GSPs treatments respectively; and control samples (SC3, SC12 and SC24) were also collected accordingly. miRNA-seq transcriptome comparisons were performed, and 26, 85 and 85 differentially expressed (DE) miRNA were identified among SS3 vs. SC3, SS12 vs. SC12 and SS24 vs. SC24 respectively, indicating the GSPs treatments could modulate the expression of miRNAs globally. Subsequently, 74, 598 and 1204 target genes of these DE miRNAs were predicted in three comparisons, and GO and KEGG analysis revealed that multiple target genes were associated with proliferation and apoptosis of PC cells. Moreover, interaction network analyis of DE miRNAs and target genes associated with PC were also carried out, and fabulous co-expression relationships further suggested that GSPs treatment could probably repress the proliferation of PC cells by modulating the miRNAs expression
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Project description:Oligomeric proanthocyanidins (OPCs) reduce triglycerides in the nematode C. elegans. Lipase was strongly inhibited in vitro accompanied by the reduction of total triglyceride storage capacity in vivo; Lipophilic staining was also attenuated in wild type worms and high-fat mutants exposed to OPCs. Apart from biochemical analyses, lipid metabolism was also genetically regulated, emphasizing the necessity to study underlying regulation mechanisms in intact animals. To gain a deeper insight into the potential gene targets of purified oligomeric proanthocyanidin trimer gallate (pOPC7), a binary microarray assay was carried out with wild type N2 populations continuously exposed to a bacterial diet with or without pOPC7.
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Project description:A "green" solvent-free industrial process (patent pending) is here described for a grape seed extract (GSE) preparation (Ecovitis™) obtained from selected seeds of Veneto region wineries, in the northeast of Italy, by water and selective tangential flow filtration at different porosity. Since a comprehensive, non-ambiguous characterization of GSE is still a difficult task, we resorted to using an integrated combination of gel permeation chromatography (GPC) and electrospray ionization high resolution mass spectrometry (ESI-HRMS). By calibration of retention time and spectroscopic quantification of catechin as chromophore, we succeeded in quantifying GPC polymers up to traces at n = 30. The MS analysis carried out by the ESI-HRMS method by direct-infusion allows the detection of more than 70 species, at different polymerization and galloylation, up to n = 13. This sensitivity took advantage of the nanoscale shotgun approach, although paying the limit of missed separation of stereoisomers. GPC and MS approaches were remarkably well cross-validated by overlapping results. This simple integrated analytical approach has been used for quality control of the production of Ecovitis™. The emerging feature of Ecovitis™ vs. a popular benchmark in the market, produced by a different technology, is the much lower content of species at low n and the corresponding increase of species at high n.
| S-EPMC8001487 | biostudies-literature
Project description:Multidrug resistance is a major hindrance in managing cancer. By performing a series of experiments in chemoresistant colorectal cancer cell lines, we demonstrate that oligomeric proanthocyanidins (OPCs) from grape seed extracts can sensitize both acquired (HCT116-FOr cells) and innately chemoresistant (H716 cells) cancer cells to chemotherapeutic drugs, 5-fluorouracil (5FU) and oxaliplatin, by inhibiting adenosine triphosphate-binding cassette (ABC) transporter proteins. When combined with chemotherapeutic drugs, OPCs significantly inhibited growth of the chemoresistant cells (P < 0.05 to < 0.001) and decreased the expression of several key ABC transporters. Moreover, the activity of the ABC transporters was also significantly decreased by OPCs in the cell lines (P < 0.05). We further confirmed that co-treatment with OPCs sensitized the chemoresistant cells to 5FU and oxaliplatin, as observed by improvement in cell cycle arrest, double-strand breaks and p53 accumulation in these cells. In addition, we confirmed that co-administration of OPCs with chemotherapeutic drugs significantly decreased chemoresistant xenograft tumor growth in mice (P < 0.05). Together, our study illuminates the downregulation of multiple ABC transporters as a mechanism by which OPCs overcome chemoresistance in cancer cells and may serve as adjunctive treatments in patients with refractory colorectal cancer.
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Project description:The influence of cranberry proanthocyanidins on the transcriptomic responses of Streptococcus mutans during biofilm formation was investigated. Treatment regimens simulating topical exposures experienced clinically (twice-daily, 60 s each) were used over saliva-coated hydroxyapatite biofilm model. Cranberry proanthocyanidins (1.5 mg/ml) in 15% ethanol was used to treat the biofilms. Four biological replicates each for the treatment and vehicle control were used for RNA extraction and microarray.
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Project description:Proanthocyanidins (PAs) that are naturally occurring compounds have shown the potential chemopreventive efficacy against various forms of cancers in different tumor models. To elucidate the responsible molecular mechanisms involved in antitumor therapeutic effects of PAs, the transcriptome changes of pancreatic cancer cells exposure to PAs at 3, 12 and 24h were investigated in this study. Through two biological replicate sequencing, 966, 3543 and 4944 differentially expressed genes in response to PAs exposure were detected at 3, 12 and 24h, respectively. GO and KEGG analysis showed that cell cycle checkpoints and DNA repair modulations or inhibition were the mainly mechanisms in PAs anti-cancer. Overall, this study provided novel insights into not only the first integrated overview on global gene expression in pancreatic cancer cells post PAs exposure, but also the underlying mechanisms of anti-cancer effects of PAs for chemotherapy.
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Project description:The influence of cranberry proanthocyanidins on the transcriptomic responses of Streptococcus mutans during biofilm formation was investigated.
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