# Proapoptotic and antimigration properties of osthole in combination with LY294002 against human glioma cells

## TL;DR

This study shows that combining osthole with LY294002 can effectively stop glioma cell migration and induce cell death.

## Contribution

The novel contribution is the first use of osthole in combination with LY294002 to inhibit glioma cell migration and induce apoptosis.

## Key findings

- The combination reduced migration by lowering metalloproteinases, Rho family proteins, and N-cadherin levels.
- The treatment induced apoptosis in glioma cells.
- Silencing Bcl-2, beclin 1, and Raf kinase supported the observed effects.

## Abstract

Anaplastic astrocytoma and glioblastoma multiforme are infiltrating and vascularized gliomas with a high degree of chemoresistance and metastasis. Our previous studies have shown that osthole may be of great importance in the treatment of gliomas. Therefore, in this work, for the first time, coumarin was used in combination with LY294002—an inhibitor of the PI3K-Akt/PKB-mTOR pathway, which is overly active in gliomas. MOGGCCM and T98G cells were incubated with osthole and LY294002, alone and in combination. Staining with specific fluorochromes was used to visualize cell death and the scratch test to assess the migration. The level of proteins was estimated by immunoblotting. Forming protrusions were visualized by SEM, and immunocytochemistry was used to determine the localization of proteins. Additionally, the expression of Bcl-2, beclin 1 and Raf kinase was silenced using specific siRNA. The obtained results showed that osthole in combination with LY294092 effectively inhibited the migration of glioma cells by reducing the level of metaloproteinases and Rho family proteins, as well as decreasing the level of N-cadherin. In addition, the combination of compounds induced apoptosis. New combination of compounds shows a high pro-apoptotic potential and also inhibits the migration of gliomas cells.