Inhibition effects of 7-phloro-eckol from Ecklonia cava on metastasis and angiogenesis induced by hypoxia through regulation of AKT/mTOR and ERK signaling pathways

Abstract

As one of the malignant tumors with high mortality, liver cancer has the characteristics of early invasion and metastasis, and lacks effective treatment methods. Therefore, it is urgent to find new safe, efficient and low-toxic anti-liver cancer drugs. In this study, the evaluated mechanism of Ecklonia cava polyphenols (7PE, 7-phloro-eckol) as a potential active substance for inhibiting liver cancer metastasis (HepG2 cell) and angiogenesis (HUVEC cell). The results have shown that 7PE can inhibit the expression of hypoxia-inducible factors (HIF-1α) protein by regulating the PI3K/AKT/mTOR and Ras/MEK/ERK/MNK signaling pathways under hypoxic conditions in HepG2 cells, thereby blocking the secretion of vascular growth factor (VEGF) protein. At the same time, 7PE can significantly inhibit the conduction of AKT and MAPK signaling pathways in HUVEC by suppressing the activation of VEGFR-2 protein, which verifies the prediction of molecular docking. Therefore, the results of this study provide a research basis for 7PE to inhibit metastasis and angiogenesis of liver cancer cells, and provide a theoretical basis for the high-value utilization of Ecklonia cava.

Keywords

• 7-phloro-eckol
• Ecklonia cava
• Hepatoma
• Hypoxia
• Metastasis
• Angiogenesis