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Effects of different forms of Anthocyanins on growth inhibition and gene expression of CRC cells

ABSTRACT: Scope: Anthocyanins from diet were found to have therapeutic potential for various cancers including colorectal cancer (CRC). Given the diverse forms of anthocyanins, it is unclear whether different types of anthocyanins share common pathways in regulating intestinal cell function. This study aims to investigate the core gene pathways modulated by anthocyanins in intestinal cells, and to identify potential compounds with similar therapeutic effects.Methods and results: Three different forms anthocyanins were used to treat CRC cells at different concentrations and time points, and growth inhibition was observed in all anthocyanins, with varying patterns. RNA-seq analysis showed that the regulatory-pathways of anthocyanins with different structures were different, and the time factor had a greater effect. Time-series analysis of regulatory-genes shared by different concentrations and structures of anthocyanins was performed. By overlapping with public PPAR target gene set, a core gene set across three types of anthocyanins was identified and used in Connectivity Map (CMap) analysis to screen for compounds. The repositioned drug candidates included known anti-cancer drugs that have effects of transcriptome interventions similar to anthocyanins.Conclusion: These findings provide new insights into the mechanisms underlying the anti-CRC effects of anthocyanins and may facilitate the development of novel therapeutic agents for CRC.

ORGANISM(S): Homo sapiens

PROVIDER: GSE242673 | GEO | 2023/09/10

REPOSITORIES: GEO

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Project description:Anthocyanins are flavonoid compounds responsible for red/purple colours in the leaves, fruit and flowers of many plant species. They are produced through a multistep pathway which is controlled by MYB transcription factors. VvMYBA1 and VvMYBA2 activate anthocyanin biosynthesis in grapevine (Vitis vinifera) and are non-functional in white grapevine cultivars. In this study, transgenic grapevines with altered VvMYBA gene expression were developed, and transcript analysis was carried out on berries using a microarray technique. The results showed that VvMYBA is a positive regulator of the later stages of anthocyanin synthesis, modification and transport in Shiraz. One up-regulated gene ANTHOCYANIN 3- O-GLUCOSIDE-6â-O-ACYLTRANSFERASE (Vv3AT) encodes a BAHD acyltransferase protein, belonging to a clade separate from most anthocyanin acyltransferases. Functional studies (in planta and in vitro) show that Vv3AT has a broad anthocyanin substrate specificity and can also utilise both aliphatic and aromatic acyl donors, a novel activity for this enzyme family found in nature. In V. vinifera cv. Pinot Noir, a red-berried grapevine mutant lacking acylated anthocyanins, Vv3AT contains a nonsense mutation encoding a truncated protein that lacks two motifs required for BAHD protein activity. Promoter activation assays confirm that Vv3AT transcription is activated by VvMYBA1, which adds to the current understanding of the regulation of the BAHD gene family. The flexibility of Vv3AT to use both classes of acyl donors will be useful in the engineering of anthocyanins in planta or in vitro. Transgenic Chardonnay/Shiraz and non-transformed WT controls were all grown in the same glasshouse in ambient light with a night break. Day and night temperatures were approximately 27oC and 22oC respectively. For microarray experiments, whole berries were sampled from independent transgenic lines: three from transgenic Chardonnay and four from transgenic Shiraz, resulting in three and four biological replicates respectively. Bunches were harvested close to ripeness based on average total soluble solids (TSS, measured as oBrix). This was aimed to be between 20 â 24 oBrix and was determined from TTS of a subsamples from each bunch (Table S53). A sample consisted of all remaining berries from a single bunch except when there were <100 berries in which case more than one bunch was used in the one replicate. Whole berries were immediately frozen in liquid nitrogen. For skin samples, the skins were first removed from fresh berries then frozen in liquid nitrogen. All samples were stored at -80oC.

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Effects of different forms of Anthocyanins on growth inhibition and gene expression of CRC cells

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