Protective effect and mechanism of Muntingia calabura Linn. fruit ethanolic extract against vascular endothelial growth factor production in nickel-stimulated hepatocellular carcinoma cells

• Published in: Journal of functional foods Vol. 47; pp. 343 - 349
• Main Authors: Lin, Jau-Tien, Chang, Yuan-Yen, Chen, Yi-Chen, Kuo, Li-Chun, Yang, Deng-Jye
• Format: Journal Article
• Language: English
• Published: Elsevier Ltd 01.08.2018; Elsevier
• Subjects: Hepatocellular carcinoma cell; Hypoxia-inducible factor (HIF)-1α; Muntingia calabura Linn; Nickel (Ni); Vascular endothelial growth factor (VEGF); Vascular endothelial growth factor (VEGF); PI3K; MEK1/2; FBS; mTOR; Muntingia calabura Linn; Ni; TEMED; Cyd-3-glu E; JAK2; MFEE; PSA; PBS; CE; SDS; HIF; Nickel (Ni); VEGF; STAT3; Hypoxia-inducible factor (HIF)-1α; AKT; GAE; EDTA; ERK1/2; Hepatocellular carcinoma cell; RAF1
• ISSN: 1756-4646; 2214-9414
• DOI: 10.1016/j.jff.2018.06.001

[Display omitted] •M. calabura Linn. fruit ethanolic extract inhibited Ni-induced VGEF expression in Hep G2 cell.•Down-regulation of PI3K/AKT/mTOR/HIF-1α pathway should be involved in the mechanism.•Down-regulation of RAF1/MEK1/2/ERK1/2 pathway should be involved in the mechanism.•Down-regulation of JAK2/STAT3 pathway should be involved in the mechanism.•The extract should have the potential to decrease liver cancer risk in Ni-polluted environment. The protective effect of the M. calabura Linn. fruit ethanolic extract (MFEE) against nickel (Ni)-induced vascular endothelial growth factor (VEGF) expression in hepatocellular carcinoma (HepG2) cells was investigated. MFEE contained 4 flavonoids: epicatechin, rutin, diosmin and luteolin, and 11 phenolic acids: gallic acid, gentisic acid, p-hydroxybenzoic acid, vanillic acid, p-coumaric acid, ferulic acid, sinapic acid, syringic acid, p-anisic acid and rosmarinic acid. Substantial VEGF expression was assayed in Ni-stimulated HepG2 cells, which was significantly suppressed through MFEE treatment via down-regulating Raf-1 proto-oncogene, serine/threonine kinase (RAF1) /mitogen-activated protein kinase 1/2 (MEK1/2)/extracellular-signal-regulated kinase 1/2 (ERK1/2), and Janus kinase 2 (JAK2)/signal transducers and activators of transcription 3 (STAT3) pathways as well as inhibiting hypoxia-inducible factor (HIF)-1α expression down-regulated by phosphatidylinositol-3-kinase (PI3K)/ protein kinase B (AKT)/mammalian target of rapamycin (mTOR) pathway. The results showed that MFEE should have the potential to lower liver cancer risk in the Ni-polluted environment by suppressing VEGF expression.