Chemopreventive and Chemotherapeutic Potential of Betulin and Betulinic Acid: Mechanistic Insights From In Vitro, In Vivo and Clinical Studies

Betulin is a bioactive compound found in large quantities in birch bark and has a triterpene pentacyclic structure. Through the oxidation of betulin, betulinic acid is obtained, which is found in large quantities in nature. Betulin and betulinic acid have multiple pharmacological properties such as antiviral, anti-inflammatory, and anticancer properties. This comprehensive review aims to deepen the knowledge of the chemopreventive and chemotherapeutic effects of betulin and betulinic acid by presenting in vitro, in vivo, and clinical studies evaluating the anticancer mechanisms of betulin, betulinic acid, and their derivatives. The databases searched using specific MESh terms to conduct this review were PubMed/MEDLINE, Web of Science, TRIP database, Wiley, and Scopus. The anticancer properties of betulin and betulinic acid have been reported in a variety of experimental pharmacological studies using different types of cancer cell lines. It has been indicated that induction of apoptosis is the primary anticancer activity of these compounds by selectively affecting cancer cells. As shown by various research, the apoptotic cell death by these compounds is mainly related to factors such as type of cancer and cancer cell line, tumor size, source of betulin/betulinic acid, dose, treatment time, and the type of the drug delivery system employed. Numerous preclinical pharmacological studies and clinical trials on the chemopreventive and antitumour effects of betulin, betulinic acid, and their derivatives have been published. Future translational pharmacological studies establishing the exact anticancer dose effective in humans are needed.