Glycosylated Delphinidins Decrease Chemoresistance to Temozolomide by Regulating NF-κB/MGMT Signaling in Glioblastoma.

in Cells by Diego Carrillo-Beltrán, Yessica Nahuelpan, Constanza Cuevas, Karen Fabres, Pamela Silva, Jimena Zubieta, Giovanna Navarro, Juan P Muñoz, María A Gleisner, Flavio Salazar-Onfray, Noemi Garcia-Romero, Angel Ayuso-Sacido, Rody San Martin, Claudia Quezada-Monrás

TLDR

  • Glycosylated delphinidins, specifically delphinidin 3,5 di-glucoside and delphinidin 3 glucoside, show promising anticancer effects against glioblastoma and may offer a natural strategy to combat TMZ resistance.

Abstract

Glioblastoma (GB) is a highly malignant brain tumor with a poor prognosis, with a median survival of only 14.6 months despite aggressive treatments. Resistance to chemotherapy, particularly temozolomide (TMZ), is a significant challenge. The DNA repair enzyme MGMT and glioblastoma stem cells (GSCs) often mediate this resistance. Recent studies highlight the therapeutic potential of natural compounds, particularly delphinidins, found in deep purple berries. Delphinidins are known for their ability to inhibit NF-κB signaling, a critical pathway for GB progression, chemoresistance, and MGMT expression. Our research demonstrates that glycosylated delphinidins have potential adjuvant use in the treatment of GB, offering a promising natural strategy to combat TMZ resistance. Specifically, we observed that delphinidin 3,5 di-glucoside has potent anticancer effects when used alone. Meanwhile, delphinidin 3 glucoside acted in synergy with temozolomide to decrease cell viability, highlighting its potential as an adjuvant. It also exerted a faster and more sustained inhibition of NF-κB, highlighting its potential for long-lasting therapeutic effects. These findings open new avenues for targeted therapies against glioblastoma, particularly to overcome treatment resistance.

Overview

  • The study focuses on the potential of delphinidins, a type of natural compound found in deep purple berries, as an adjuvant therapy for glioblastoma (GB) to combat TMZ resistance.
  • The researchers investigated the efficacy of glycosylated delphinidins, specifically delphinidin 3,5 di-glucoside and delphinidin 3 glucoside, in inhibiting NF-κB signaling and GB cell viability.
  • The primary objective of the study is to explore the therapeutic potential of delphinidins as a natural strategy to overcome treatment resistance in GB patients.

Comparative Analysis & Findings

  • Delphinidin 3,5 di-glucoside demonstrated potent anticancer effects when used alone, indicating its potential as a standalone therapeutic agent.
  • Delphinidin 3 glucoside showed synergistic effects with temozolomide, leading to decreased cell viability and highlighting its potential as an adjuvant therapy.
  • Both glycosylated delphinidins exhibited stronger and more sustained NF-κB inhibition compared to delphinidin alone, suggesting their potential for long-lasting therapeutic effects.

Implications and Future Directions

  • The study's findings suggest that delphinidins, particularly glycosylated forms, could be a promising natural strategy to overcome treatment resistance in GB patients.
  • Further research is needed to explore the optimal dosing and combination regimens of delphinidins with standard TMZ-based chemotherapy to maximize therapeutic efficacy.
  • Future studies could investigate the potential of delphinidins in combination with other targeted therapies to develop more effective treatment strategies for GB patients.
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