Reduction of metastatic and angiogenic potency of malignant cancer by Eupatorium fortunei via suppression of MMP-9 activity and VEGF production

Abstract

Eupatorium fortunei has long been used to treat nausea and poor appetite, and has been prescribed as a diuretic and detoxifying drug in Chinese medicine. Recent studies have demonstrated that E. fortunei possesses anti-bacterial, anti-oxidant, and anti-diabetic activities, as well as cytotoxicity to human leukemia cells. However, at non-toxic concentrations, the effects of an aqueous extract of E. fortunei (WEF) on the metastatic and angiogenic potential of malignant tumor cells have not been reported. In this study, we found that WEF suppressed the metastatic properties, including anchorage-independent colony formation, migration, and invasion, by downregulating the proteolytic activity of MMP-9. NF-κB activation and the phosphorylation of p38 and JNK were reduced significantly by WEF. Additionally, WEF inhibited tumor-induced angiogenesis markedly, affecting HUVEC migration, tube formation by HUVECs, and microvessel sprouting from rat aortic rings via a reduction in VEGF in tumors. In a pulmonary metastasis model, daily administration of WEF at 50 mg/kg markedly decreased metastatic colonies of intravenously injected B16F10 cells on the lung surface in C57BL/6J mice. Further, none of the WEF-administered mice exhibited systemic toxicity. Taken together, our results indicate that WEF is a potential therapeutic herbal product that may be useful for controlling malignant metastatic cancer.

Ethanol extract of Lophatheri Herba exhibits anti-cancer activity in human cancer cells by suppression of metastatic and angiogenic potential

“…As reported previously4445, CM from HT1080 cells dramatically promoted migration across Transwells and tube-like network formation on the Matrigel of HUVECs and increased the sprouting of microvessels from aortic rings; CM from ELH-treated HT1080 cells induced these changes to a lesser extent and caused no cytotoxicity (Fig. 6A–C).…”

Sigma-2 Receptors Play a Role in Cellular Metabolism: Stimulation of Glycolytic Hallmarks by CM764 in Human SK-N-SH Neuroblastoma

“…HIF1a allows cells to overcome hypoxic conditions, which are common in the core of tumors and for metastases that may not have an established blood supply. Furthermore, through its transcriptional activation of VEGF, HIF1a promotes angiogenesis, and therefore oxygen supply for metastatic sites (Lin et al, 2004;Liang et al, 2008;Kim et al, 2014). The novel function of the sigma-2 receptor that our study has revealed is consistent with this role of HIF1a in rapidly proliferating cancer cells and allows for congruous explanation of the high expression of sigma-2 receptors in the same.…”

Anti-tumor and anti-invasion effects of a combination of 4-methylumbelliferone and ionizing radiation in human fibrosarcoma cells

“…Abnormal secretion of HA has been observed in malignant tumors (18), however, HA is required in normal tissue, therefore, it is important to clarify the regulating system for HA secretion. Kim et al (19) have reported that suppression of MMP-9 activity and vascular endothelial growth factor production in malignant tumor cells reduces tumor metastasis and angiogenic potency. In addition, Rauhala et al (20) have demonstrated that keratinocytes exposed to low-dose UVB radiation increased HA synthesis with the production of ROS.…”