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

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