Blueberry Malvidin-3-galactoside Suppresses Hepatocellular Carcinoma by Regulating Apoptosis, Proliferation, and Metastasis Pathways In Vivo and In Vitro.

Abstract

Anthocyanin, a natural antioxidant, is reported to have cytotoxicity against cancer cells; however, the mechanism remains unclear. The aim of the present study was to investigate the mechanism by which malvidin-3-galactoside (M3G), the prominent anthocyanin in blueberry, suppresses the development of hepatocellular carcinoma. In vitro, M3G suppressed the proliferation, polarization, migration, and invasion activities of HepG2 cells by regulating the protein expression of cyclin D1, cyclin B, cyclin E, caspase-3, cleaved caspase-3, Bax, p-JNK, and p-p38, activating phosphatase and tensin homologue deleted on chromosome 10 (PTEN), accompanied by a decrease in the p-AKT level, and lowering the protein expression levels of MMP-2 and MMP-9. In vivo, M3G promoted the apoptosis of liver tumor cells, as determined by immunohistochemistry (cleaved caspase-3, Ki-67, PTEN, and p-AKT), a terminal deoxynucleotidyl transferase dUTP nick end labeling assay, and hematoxylin-eosin staining. Overall, these results suggest that M3G, as an adjuvant ingredient or nutritional supplement, may be beneficial for liver cancer prevention and the modulatory mechanism seems to be associated with inhibition of proliferation, apoptosis, migration, and invasion-related pathways.

• Authors: Yuehua Wang, Jie Lin, Jinlong Tian, Xu Si, Xinyao Jiao, Weijia Zhang, Ersheng Gong, Bin Li
• Journal: Journal of agricultural and food chemistry (J Agric Food Chem) Vol. 67 Issue 2 Pg. 625-636 (Jan 16 2019) ISSN: 1520-5118 [Electronic] United States
• PMID: 30586992 (Publication Type: Journal Article)

Chemical References

• Anthocyanins
• Plant Extracts
• PTEN Phosphohydrolase
• PTEN protein, human
• CASP3 protein, human
• Caspase 3
• Matrix Metalloproteinase 2
• Matrix Metalloproteinase 9
• malvidin 3-galactoside

Topics

• Animals
• Anthocyanins (administration & dosage)
• Apoptosis (drug effects)
• Blueberry Plants (chemistry)
• Carcinoma, Hepatocellular (drug therapy, genetics, metabolism, physiopathology)
• Caspase 3 (genetics, metabolism)
• Cell Line, Tumor
• Cell Movement
• Cell Proliferation (drug effects)
• Fruit (chemistry)
• Hep G2 Cells
• Humans
• Liver Neoplasms (drug therapy, genetics, metabolism, physiopathology)
• Male
• Matrix Metalloproteinase 2 (genetics, metabolism)
• Matrix Metalloproteinase 9 (genetics, metabolism)
• Mice
• Mice, Inbred C57BL
• Neoplasm Metastasis (drug therapy, genetics)
• PTEN Phosphohydrolase (genetics, metabolism)
• Plant Extracts (pharmacology)
• Signal Transduction (drug effects)