Antimetastatic Effects of Gambogic Acid are Mediated via the Actin Cytoskeleton and NF‐κB Pathways in SK‐HEP1 Cells

Abstract

Hepatocellular carcinoma (HCC) is one of the most malignant and frequent cancers with a high metastatic potential. The prevention of HCC metastasis is a critical target for effective therapies in HCC. Gambogic acid (GA), a natural compound obtained from Garcinia hanburyi has reported anticancer activity in cell lines. However, the antimetastatic mechanisms of GA are unclear, particularly with respect to HCC. In this study, the influence of GA on migration and invasion of SK-HEP1 cells was evaluated. At concentrations above 0.6 μM, GA reduced cell proliferation in SK-HEP1 cells without affecting proliferation of noncancerous HEK-293 cells. GA also suppressed migration and invasion of SK-HEP1 cells. GA downregulated the expression of the integrin β1/rho family GTPase signaling pathway, suppressed the actin rearrangement related to cell cytoskeleton and migration and decreased matrix metalloproteinases MMP-2, MMP-9, and NF-κB expression involved in cancer invasion. These results suggest that GA may be a potential lead in developing an antimetastatic therapeutic for the treatment of HCC.

Actinidia callosa var. callosa suppresses metastatic potential of human hepatoma cell SK-Hep1 by inhibiting matrix metalloproteinase-2 through PI3K/Akt and MAPK signaling pathways

“…SK-Hep1 is an immortal, human cell line derived from the ascetic fluid of a patient with liver adenocarcinoma. High metastatic capacities of SK-Hep1 cells are suitable for cancer metastasis research and have been used wildly in the literature (Park et al 2015 ). In this study we examined the antimetastatic effects of EAAC in human hepatoma SK-Hep1 cells.…”

Gambogic acid exerts cardioprotective effects in a rat model of acute myocardial infarction through inhibition of inflammation, iNOS and NF‑κB/p38 pathway

“…The present study found that treatment with gambogic acid significantly inhibited MMP-2 and MMP-9 protein expression in cardiac tissues of AMI rats. Park et al (14) suggested that gambogic acid decreased MMP-2, MMP-9 and NF-κB expression in SK-HEP1 cells.…”

“…The anti-tumor effects of gambogic acid are extensive and include the induction of tumor cell apoptosis, inhibition of the cell cycle, and an influence on the expression of certain oncogenes, cancer suppressor genes and associated proteins (13). As an anti-tumor drug, gambogic acid has an obvious inhibitory effect on the growth of tumors grown in animal models, but anti-tumor drugs often generate untoward effects and easily cause irreversible damage to the hemopoietic and immune system (14). In the present study, a rat model of AMI was used to investigate the protective effects of gambogic acid and their possible association with inhibition of inflammation via the iNOS and nuclear factor (NF)-κB/p38 pathways.…”

Steroid receptor coactivator-3 is a pivotal target of gambogic acid in B-cell Non-Hodgkin lymphoma and an inducer of histone H3 deacetylation

“…In recent decades, both in vitro and in vivo evidence revealed the potent anti-tumor efficacies of GA, not only in solid tumors Ishaq et al, 2014;Zhao et al, 2008;Park et al, 2015), but also in hematological malignancies (Gupta et al, 2010;Prasad et al, 2011;Yang and Chen, 2013). However, the anti-tumor efficacies of GA in B-cell NHL and the underlying mechanism have not been fully uncovered.…”