Umbelliprenin Inhibited Angiogenesis and Metastasis of MDA-MB-۲۳۱ Cell Line through Downregulation of CoCl۲ / EGFMediated PI۳K / AKT / ERK Signaling

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 PI۳K / Akt / ERK signaling pathway and their products HIF-۱α / VEGF in the MDA-MB-۲۳۱ cell line.Method: In this experimental study, the cytotoxic effect of UMB on MDA-MB- ۲۳۱ cells was evaluated using the MTT assay and the UMB concentrations of IC۵ and IC۱۰ were selected for the signaling pathway study. MDA-MB-۲۳۱ cells were stimulated with EGF and CoCl۲ and UMB IC۵ and IC۱۰ effects on gene expression and translation was studied. PI۳K / Akt / mTOR / S۶K / Erk۱ and ۲ / ۴E-BP۱ / HIF-۱α / HIF-۱α/ EGFR / VEGFR and VEGF mRNA expression, and VEGF / HIF-۱α proteins were evaluated employing real time polymerase chain reaction and western blot analysis, respectively.Results: The concentrations of UMB in IC۱۰ and IC۵ were ۲۰ and ۱۰ μM, respectively. UMB, specifically IC۱۰, significantly inhibited PI۳K, ERK۱, ERK۲, Akt, mTOR, HIF۱-α, HIF۱-β mRNA, as well as HIF-۱α and VEGF protein expression. Conclusion: Our results suggested that UMB, a cytotoxic agent, inhibits PI۳K / Akt / ERK signal pathway in the CoCl۲ or EGF-stimulated MDA-MB-۲۳۱ cells.

کلیدواژه ها:

Umbelliprenin ، MDA-MB-۲۳۱ ، Cobalt Chloride ، EGF ، HIF۱α ، VEGF ، Angiogenesis ، cancer