Therapeutic Potential of Annona muricata (Graviola) in Cancer Management: Current Evidence, Safety Considerations and Future Prospects

Annona muricata L., colloquially designated as graviola or soursop, represents a tropical botanical species of significant pharmacological interest due to its diverse array of secondary metabolites and associated bioactivities. This narrative review critically evaluates the extant literature regarding its botanical taxonomy, phytochemical profile, preclinical oncological investigations, underlying molecular mechanisms, toxicological parameters, and current research constraints, while outlining strategic imperatives for future inquiry. Prominent analytical focus is directed toward annonaceous acetogenins—specifically annonacin and its structural analogues—alongside endogenous alkaloids, phenolic compounds, and flavonoids. Although in vitro and in vivo models demonstrate that these constituents modulate neoplastic cell viability, proliferative pathways, apoptotic biomarkers, cell-cycle checkpoints, and mitochondrial integrity, these preliminary outcomes remain strictly hypothesis-generating and do not constitute definitive evidence of clinical efficacy in human subjects. Comparative evaluation of the literature is profoundly challenged by systemic heterogeneities, including variations in anatomical plant parts, geographical provenance, extraction menstrua, processing methodologies, phytochemical yields, and experimental protocols. Furthermore, the potent mitochondrial disruption mediated by select acetogenins raises critical questions regarding cellular selectivity, suggesting that cytotoxicity may extend to non-malignant tissue. Concurrently, documented toxicological risks and unresolved questions surrounding prolonged exposure, potential neurotoxicity, standardized product quality, and herb-drug interactions necessitate pronounced clinical vigilance. While the reviewed data underscore the utility of authenticated botanical material and chemically profiled isolates as potential scaffolds for novel drug discovery, clinical advancement remains contingent upon strict analytical standardization, bioassay-guided isolation, comparative toxicity screening against normal cell lines, pharmacokinetic profiling, and comprehensive toxicological assays. Consequently, current empirical evidence is insufficient to validate A. muricata or its commercial derivatives as safe or effective antineoplastic modalities; thus, their use must not supplant, defer, or compromise standard, evidence-based oncological care. Any future translational evaluation demands chemically characterized matrices, a rigorous preclinical safety portfolio, and ethically approved clinical protocols.