Mangosteen for malignancy prevention and intervention: Current evidence, molecular mechanisms, and future perspectives

Mangosteen (Garcinia mangostana L.), also known as the "queen of fruits", is a tropical fruit of the Clusiacea family. While native to Southeast Asian countries, such as Thailand, Indonesia, Malaysia, Myanmar, Sri Lanka, India, and the Philippines, the fruit has gained popularity in the United States due to its health-promoting at-tributes. In traditional medicine, mangosteen has been used to treat a variety of illnesses, ranging from dysentery to wound healing. Mangosteen has been shown to exhibit numerous biological and pharmacological activities, such as antioxidant, anti-inflammatory, antibacterial, antifungal, antimalarial, antidiabetic, and anticancer properties. Disease-preventative and therapeutic properties of mangosteen have been ascribed to secondary metabolites called xanthones, present in several parts of the tree, including the pericarp, fruit rind, peel, stem bark, root bark, and leaf. Of the 68 mangosteen xanthones identified so far, the most widely-studied are alpha-mangostin and gamma-mangostin. Emerging studies have found that mangosteen constituents and phytochemicals exert encouraging antineoplastic effects against a myriad of human malignancies. While there are a growing number of individual research papers on the anticancer properties of mangosteen, a complete and critical evaluation of published experimental findings has not been accomplished. Accordingly, the objective of this work is to present an in-depth analysis of the cancer preventive and anticancer potential of mangosteen constituents, with a special emphasis on the associated cellular and molecular mechanisms. Moreover, the bioavailability, pharmacokinetics, and safety of mangosteen-derived agents together with current challenges and future research avenues are also discussed.