α-Mangostin, a xanthone derivative extracted from the pericarp of the mangosteen fruit (Garcinia mangostana L.), has garnered significant attention for its potential as a natural anti-cancer agent. This review provides a comprehensive analysis of the current literature on the anti-cancer properties of α-mangostin across various cancer types. Through an extensive analysis of in vitro and in vivo studies, this review elucidates the multifaceted mechanisms underlying α-mangostin's cytotoxicity, apoptosis induction through both intrinsic and extrinsic pathways, and modulation of key cellular processes implicated in cancer progression in a diverse array of cancer cells. It causes mitochondrial dysfunction, activates caspases, and regulates autophagy, endoplasmic reticulum stress, and oxidative stress, enhancing its anti-cancer efficacy. Moreover, α-mangostin exhibits synergistic effects with conventional chemotherapeutic agents, suggesting its utility in combination therapies. The ability of α-mangostin to inhibit cell proliferation, modulate cell cycle progression, and induce apoptosis is linked to its effects on key signaling pathways, including Akt, NF-κB, and p53. Preclinical studies highlight the therapeutic potential and safety profile of α-mangostin, demonstrating significant tumor growth inhibition without adverse effects on normal cells. In summary, understanding the molecular targets and mechanisms of action of α-mangostin is crucial for its development as a novel chemotherapeutic agent, and future clinical investigations are warranted to explore its clinical utility and efficacy in cancer prevention and therapy.
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