The in vitro antitumor activity of Siegesbeckia glabrescens against ovarian cancer through suppression of receptor tyrosine kinase expression and the signaling pathways

Abstract

Siegesbeckia glabrescens (SG) Makino (Compositae) has been used as a traditional medicine for the treatment of a variety of diseases such as allergy, inflammation, acute hepatitis and hypertension. The primary aim of this study was to determine whether the ethanol extract of SG has antitumor activity against ovarian cancer and to identify molecular mechanisms and targets involved in the regulation of cell growth and progression. We demonstrate that SG treatment inhibits proliferation, adhesion, migration and invasion of SKOV-3 human ovarian cancer cells. The anti-proliferative effect of SG on SKOV-3 cells is accompanied by reduced expression of cyclin E and enhanced expression of the cyclin-dependent kinase inhibitor p27Kip1, leading to inhibition of pRb phosphorylation. We also show that these antitumor activities are found to be mediated through suppression of FAK, ERK, Akt and p70S6K-dependent signaling pathways and downregulation of receptor tyrosine kinases such as EGFR, VEGFR-2 and FGFR-1 as well as the cell adhesion molecule N-cadherin. Taken together, our findings suggest further development and evaluation of SG for the treatment of ovarian cancer.