Umbelliprenin Inhibited Angiogenesis and Metastasis of MDA-MB-231 Cell Line through Downregulation of CoCl2 / EGF-Mediated PI3K / AKT / ERK Signaling

Abstract

Background: Breast cancer is known to be one of the most prevalent malignancies in women worldwide. Umbelliprenin is a naturally-occurring component derived from plant species, which has shown anti-cancer properties. The present study aimed to evaluate the effect of umbelliprenin on the PI3K / Akt / ERK signaling pathway and their products HIF-1α / VEGF in the MDA-MB-231 cell line. Method: In this experimental study, the cytotoxic effect of umbelliprenin on MDA-MB-231 cells was evaluated using the MTT assay and the umbelliprenin concentrations of IC5 and IC10 were selected for the signaling pathway study. MDA-MB-231 cells were stimulated with EGF and CoCl2 and umbelliprenin IC5 and IC10 effects on gene expression and translation was studied. PI3K / Akt / mTOR / S6K / Erk1 and 2 / 4E-BP1 / HIF-1α / HIF-1β / EGFR / VEGFR and VEGF mRNA expression, and VEGF / HIF-1α proteins were evaluated employing real time PCR and western blot analysis, respectively. Results: The concentrations of umbelliprenin in IC10 and IC5 were 20 and 10 μM, respectively. Umbelliprenin, specifically IC10, significantly inhibited PI3K, ERK1, ERK2, Akt, mTOR, HIF1-, HIF1- mRNA, as well as HIF-1 and VEGF protein expression. Conclusion: Our results suggested that UMB, a cytotoxic agent, inhibits PI3K / Akt / ERK signal pathway in the CoCl2 or EGF-stimulated MDA-MB-231 cells.