Metabolic and Regulatory Pathways Involved in the Anticancer Activity of Perillyl Alcohol: A Scoping Review of In Vitro Studies

Abstract

Background/Objectives: Perillyl alcohol (POH), a plant-derived compound, has demonstrated anti-tumor activity across various human cancers. Understanding the regulatory pathways through which POH exerts its effects is crucial for identifying new therapeutic opportunities and exploring potential drug repositioning strategies. Therefore, this scoping review aims to provide a comprehensive overview of the metabolic and regulatory pathways involved in the anticancer effects of POH, based on in vitro evidence. Methods: Following the PRISMA-ScR 2018 guidelines, a systematic search was conducted in the PUBMED, Web of Science, and Scopus databases. Results: A total of 39 studies were included, revealing that POH exerts its biological effects by modulating several pathways, including the regulation of cyclins, CDKs, and p21, thereby affecting cell cycle progression. It inhibits growth and promotes cell death by attenuating AKT phosphorylation, reducing PARP-1 activity, increasing caspase activity and the FAS receptor and its ligand FASL. Additionally, POH reduces ERK phosphorylation, inhibits RAS protein isoprenylation, and decreases Na/K-ATPase activity. Conclusions: In conclusion, this review delineates the key regulatory pathways responsible for mediating the biological effects of POH in cancer.