Effects of Galium aparine Extract on the Angiogenic Cytokines and ERK1/2 proteins in Human Breast Cancer Cells

Year 2017, Volume: 13 Issue: 1, 171 - 179, 01.03.2017

Harika Atmaca

Abstract

Tumor
angiogenesis is a multiple step process regulated by a range of pro- and
anti-angiogenic factors, cytokines and several signaling cascades, including
the ERK1/2 MAP kinase pathway. Galium aparine (GA) is a perennial plant of the
family Rubiaceae, growing widespread in Anatolia. It has been shown that GA
methanol (MeOH) extract has anti-proliferative and apoptotic effects on human
breast cancer cells. To investigate the underlying mechanisms that might
account for the anti-proliferative effect of GA extract, changes in angiogenic
cytokines and ERK1/2 proteins were investigated in human MCF-7 and MDA-MB-231
breast cancer cells. Viability of breast cancer cells after treatment of GA
were determined by Cell Proliferation Kit II. Changes in angiogenic cytokines
in breast cancer cells was done by a Human Angiogenesis Antibody Array. Protein
levels of phospho ERK1 and 2 were evaluated by western blot analysis. GA
induced cytotoxicity and apoptosis in a time- and concentration-dependent
manner in both cancer cells. Dipeptidyl peptidase-4 (DPPIV), insulin-like
growth factor-binding protein 1 (IBP-1) and transforming growth factor beta 1
(TGF-β1) levels were significantly decreased; however, secretion of serpin E1
was significantly increased by GA extract in MCF-7 cells. In MDA-MB-231 cells,
the levels of amphiregulin (AR), interleukin 8 (IL-8), insulin-like growth
factor-binding protein 3 (IBP-3), metalloproteinase-8 (MMP-8), heparin-binding
EGF-like growth factor (HB-EGF) and platelet-derived growth factor (PDGF) were
decreased by GA extract treatment. The secretion of pro-angiogenic cytokines
such as neuregulin-1 (NRG1-β1), vascular endothelial growth factor (VEGF) and
tissue factor (TF) were significantly decreased by GA treatment in both breast
cancer cells. There was also a significant decrease in protein levels of both
ERK1 and ERK2 in MCF-7 and MDA-MB-231 breast cancer cells by GA treatment.
These data suggest that GA might be a promising candidate for anti-tumor and
anti-angiogenic treatment of breast cancer.

Keywords

Angiogenic cytokines, breast cancer cells, ERK1, ERK2, Galium aparine

References

• Kirsch, M.; Schackert, G.; Black, P.M. Metastasis and angiogenesis. Cancer. Treat. Res. 2004; 117, 285-304.