Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives
Open Access
- 9 February 2024
- journal article
- review article
- Published by MDPI AG in International Journal of Molecular Sciences
- Vol. 25 (4) , 2108
Abstract
Betulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well as through chemical synthesis or microbial biotransformation. Betulinic acid has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, and antioxidant activities. Notably, its ability to cross the blood–brain barrier addresses a significant challenge in treating neurological pathologies. This review aims to compile information about the impact of betulinic acid as an antitumor agent, particularly in the context of glioblastoma. Importantly, betulinic acid demonstrates selective antitumor activity against glioblastoma cells by inhibiting proliferation and inducing apoptosis, consistent with observations in other cancer types. Compelling evidence published highlights the acid’s therapeutic action in suppressing the Akt/NFκB-p65 signaling cascade and enhancing the cytotoxic effects of the chemotherapeutic agent temozolomide. Interesting findings with betulinic acid also suggest a focus on researching the reduction of glioblastoma’s invasiveness and aggressiveness profile. This involves modulation of extracellular matrix components, remodeling of the cytoskeleton, and secretion of proteolytic proteins. Drawing from a comprehensive review, we conclude that betulinic acid formulations as nanoparticles and/or ionic liquids are promising drug delivery approaches with the potential for translation into clinical applications for the treatment and management of glioblastoma.Keywords
Funding Information
- Fundação para a Ciência e a Tecnologia (UIDB/50006/2020)
This publication has 98 references indexed in Scilit:
- New Horizons for Old Drugs and Drug LeadsJournal of Natural Products, 2014
- Phytochemical profile of Rosmarinus officinalis and Salvia officinalis extracts and correlation to their antioxidant and anti-proliferative activityFood Chemistry, 2013
- New ionic derivatives of betulinic acid as highly potent anti-cancer agentsBioorganic & Medicinal Chemistry Letters, 2012
- Betulinic acid inhibits high glucose‐induced vascular smooth muscle cells proliferation and migrationJournal of Cellular Biochemistry, 2010
- Pentacyclic Triterpenes of the Lupane, Oleanane and Ursane Group as Tools in Cancer TherapyPlanta Medica, 2009
- A Short Enantioselective Total Synthesis of the Fundamental Pentacyclic Triterpene LupeolJournal of the American Chemical Society, 2009
- Characterization of NVX‐207, a novel betulinic acid‐derived anti‐cancer compoundEuropean Journal of Clinical Investigation, 2009
- A Concise Semi-Synthetic Approach to Betulinic Acid from BetulinSynthetic Communications, 1997
- On the Antibacterial Action of Cultures of a Penicillium, with Special Reference to Their Use in the Isolation of B. influenzaeClinical Infectious Diseases, 1980
- Total synthesis of lupeolJournal of the American Chemical Society, 1971