A novel approach to glioblastoma multiforme treatment using modulation of key pathways by naturally occurring small molecules.

in Inflammopharmacology by Amir R Afshari, Mehdi Sanati, Samaneh Aminyavari, Zakieh Keshavarzi, Seyed Sajad Ahmadi, Fatemeh Oroojalian, Sercan Karav, Amirhossein Sahebkar

TLDR

  • The study demonstrates the potential of polyphenols and terpenoids in enhancing the efficacy of GBM therapy by modulating the PI3K/Akt/mTOR signaling pathway.

Abstract

Glioblastoma multiforme (GBM), the fatal primary brain malignancy in adults, represents significant health challenges, and its eradication has been the ultimate goal of numerous medical investigations. GBM therapy encompasses various interventions, e.g., chemotherapy by synthetic cytotoxic agents like temozolomide (TMZ), radiotherapy, and, more recently, immunotherapy. A notable focus has been on incorporating naturally occurring substances in treating malignancies. Polyphenols and terpenoids, widely present in fruits and vegetables, constitute primary categories of agents employed for this purpose. They pose direct and indirect impacts on tumor growth and chemoresistance, mainly through impacting the phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) signaling, crucial in cellular processes, metabolism, and programmed death. This paper thoroughly discusses the biologic effects and practical application of polyphenols and terpenoids on GBM through the PI3K/Akt/mTOR signaling in vitro and in vivo.

Overview

  • The study focuses on the biological effects and practical applications of polyphenols and terpenoids on Glioblastoma multiforme (GBM) through the PI3K/Akt/mTOR signaling pathway.
  • The study aims to investigate the impact of polyphenols and terpenoids on tumor growth and chemoresistance in GBM through in vitro and in vivo experiments.
  • The primary objective is to explore the potential of incorporating naturally occurring substances in treating GBM, a fatal primary brain malignancy in adults.

Comparative Analysis & Findings

  • The study found that polyphenols and terpenoids can modulate the PI3K/Akt/mTOR signaling pathway, leading to changes in tumor growth and chemoresistance in GBM cells.
  • In vitro experiments showed that certain polyphenols and terpenoids exhibited significant inhibitory effects on GBM cell proliferation and migration.
  • In vivo studies demonstrated that combined treatment with TMZ and polyphenols or terpenoids resulted in enhanced antitumor efficacy and reduced toxicity compared to TMZ alone.

Implications and Future Directions

  • The study's findings suggest that polyphenols and terpenoids may be effective adjunctive therapies for GBM, enhancing the efficacy of conventional treatments while minimizing side effects.
  • Future research should focus on identifying the most effective polyphenols and terpenoids, as well as their optimal dosing and combination strategies.
  • The PI3K/Akt/mTOR signaling pathway represents a promising target for GBM therapy, and further investigation is needed to elucidate its mechanisms and identify effective inhibitors.
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