Document Type : Original Article

Authors

1 Department of Clinical Biochemistry, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

2 Department of Medical Genetics, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

3 Department of Pharmacology, School of Medicine, Shahid Beheshti University of Medical Sciences, Tehran, Iran

10.30476/mejc.2021.86492.1347

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.

Keywords

This article has been accepted for publication and undergone full peer review but has not been through the copyediting, typesetting, pagination, and proofreading process, which may lead to differences between this version and the Version of Record. Please cite this article as doi:10.30476/mejc.2021.86492.1347