# Pleiotropic Effects of 3-O-Decanoylquercetin on U373-MG Human Glioma Cell Line

## TL;DR

A new quercetin derivative, Q-3-Dec, shows promise in fighting glioma brain tumors by targeting multiple survival pathways in cancer cells.

## Contribution

The study identifies Q-3-Dec as a multi-target agent that simultaneously disrupts key survival signals and DNA repair mechanisms in glioma cells.

## Key findings

- Q-3-Dec treatment caused significant morphological changes and mitochondrial dysfunction in U373-MG glioma cells.
- Q-3-Dec reduced NF-κB and STAT3 signaling, along with anti-apoptotic proteins and MGMT expression.
- Exposure to Q-3-Dec led to approximately 30% cell death in glioma cells after 48 hours.

## Abstract

Gliomas are among the most challenging brain tumors to treat, owing to their marked heterogeneity and the aberrant signaling networks that sustain tumor growth and resistance to therapy. Quercetin, a dietary flavonoid widely found in fruit and vegetables, exhibits documented anticancer activity, prompting the development of optimized derivatives with improved biological potency. In earlier work, we synthesized and evaluated a series of quercetin derivatives and identified the acylated compound 3-O-decanoylquercetin (Q-3-Dec) as particularly effective in reducing glioma cell viability. In this study, we explored Q-3-Dec as a multi-target agent, which concomitantly impairs NF-κB/STAT3-dependent survival signaling, mitochondrial function, and O6-Methylguanine-DNA Methyltransferase (MGMT) expression, a DNA repair enzyme closely associated with chemoresistance, in glioma cells. In U373-MG glioma cells, treatment with 50 μM Q-3-Dec triggered pronounced, time-dependent morphological changes and an early loss of mitochondrial membrane potential after 3 h. With prolonged exposure, Q-3-Dec markedly decreased NF-κB and STAT3 phosphorylation and reduced the expression of the anti-apoptotic proteins Bcl-2 and survivin, alongside a significant decrease in MGMT levels. These combined effects culminated in a progressive increase in cell death, reaching approximately 30% after 48 h. Together, these findings position Q-3-Dec as a multi-node modulator of glioma survival, supporting its potential for further preclinical development to improve future therapeutic strategies against glioma.