Abstract

The objective of this study was to evaluate the anti-proliferation and inducing apoptosis of human hepatocellular carcinoma HepG-2 cells by anthocyanin. In order to investigate the involvement of apoptotic-related proteins and gene expression, RT-PCR, western blot, transcriptome sequencing, and appropriate biochemical assays were employed. The results indicated that anthocyanin showed significant inhibitory effect on HepG-2 cells (p < 0.05). Anthocyanin induced cell apoptosis in HepG-2 cells, increased in the generation of reactive oxygen species, decreased mitochondrial membrane potential, increased the activity caspase-3, released cytochrome c from the mitochondria into the cytosol, down-regulated the expression of Bcl-2, and up-regulated the expression of Bax. The transcriptome sequencing analysis revealed that anthocyanin activated p38 MAPK signal pathway, p53 signaling pathway and apoptotic signaling pathway in response to endoplasmic reticulum stress and inactivated TGF-beta signaling pathway. Genes involved in apoptosis included GADD45A, GADD45B, DDIT4, CHAC1, ATF-4, CDKN1A, and EPHA2. The present findings indicated that anthocyanin from blueberry can significantly induce HepG-2 cells apoptosis and might be used as an adjuvant ingredient for cancer prevention in the future.

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