Grape seed proanthocyanidins inhibit proliferation of pancreatic cancer cells by modulating microRNA expression.

MicroRNAs (miRNAs) are small non-coding RNAs of 18-25 nucleotides that modulate gene expression at the post-transcriptional level. Grape seed proanthocyanidins (GSPs), which are biologically active components in grape seeds, have been demonstrated to exhibit anticancer effects. The current study investigated whether GSPs can regulate miRNA expression and the possible anticancer molecular mechanisms of GSPs. Pancreatic cancer (PC) cell samples, SS3, SS12 and SS24, were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control samples, SC3, SC12 and SC24, were also prepared. Using miRNA-seq, transcriptome analysis identified 24, 83 and 83 differentially expressed (DE) miRNAs in SS3 vs. SC3, SS12 vs. SC12 and SS24 vs. SC24, respectively. This indicated that treatment with GSPs could modulate the expression of miRNAs. Subsequently, 74, 598 and 1,204 target genes for the three sets of DE miRNAs were predicted. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes analysis revealed that multiple target genes were associated with the proliferation and apoptosis of PC cells. In addition, a network was constructed of the DE miRNAs and the target genes associated with PC. The associations identified suggested that treatment with GSPs may inhibit the proliferation of PC cells through the modulation of miRNA expression.

Transcriptome analysis of pancreatic cancer cell response to treatment with grape seed proanthocyanidins.

Grape seed proanthocyanidins (GSPs) have been demonstrated to exhibit potential chemotherapeutic efficacy against various cancer types. To determine the underlying molecular mechanisms involved in GSP-induced apoptosis, the present study prepared pancreatic cancer (PC) cells samples, S3, S12 and S24, which were treated with 20 µg/ml GSPs for 3, 12 and 24 h, respectively. Control cell samples, C3, C12 and C24, were also prepared. Using RNA-sequencing, transcriptome comparisons were performed, which identified 966, 3,543 and 4,944 differentially-expressed genes (DEGs) in S3 vs. C3, S12 vs. C12 and S24 vs. C24, respectively. Gene Ontology analysis of the DEGs, revealed that treatment with GSPs is associated with disruption of the cell cycle (CC) in PC cells. Additionally, disruption of transcription, DNA replication and DNA repair were associated with GSP-treatment in PC cells. Network analysis demonstrated that the common DEGs involved in the CC, transcription, DNA replication and DNA repair were integrated, and served essential roles in the control of CC progression in cancer cells. In summary, GSPs may exhibit a potential chemotherapeutic effect on PC cell proliferation.