Document Type : Original Article


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


Background: 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.
Method: 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.
Results: 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.
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.


How to cite this article:

Mahmoodi Khatonabadi S, Salami S, Mirfakhraie R, Atabakhshian R, Sirati-Sabet M, Gholamali Yaghmaei B, et al. Umbelliprenin inhibited angiogenesis and metastasis of MDA-MB-231 cell line through downregulation of CoCl2 / EGF-mediated PI3K / AKT / ERK signaling. Middle East J Cancer. 2022;13(2):226-36-p. doi: 10.30476/mejc.2021. 86492.1347.

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