Anticancer Potential of Mangifera indica Leaves and Mangiferin: Phytochemistry, Mechanistic Evidence and Therapeutic Translation

Abstract

Mango (Mangifera indica L.) leaves contain a chemically heterogeneous mixture of xanthones, benzophenones, gallotannins, phenolic acids and flavonoids. Mangiferin, a C-glucosylxanthone occurring in these leaves and other botanical sources, has attracted investigation as an experimental anticancer agent. This critical narrative review distinguishes the activity of chemically characterised leaf preparations from that of isolated mangiferin and examines whether preclinical mechanistic findings can plausibly translate into cancer treatment. Peer-reviewed original investigations and relevant reviews published through 28 August 2026 were selected from accessible scholarly sources, with emphasis on chemical authentication, biological controls, mechanistic specificity, combination effects, systemic exposure and study design. Leaf-extract studies suggest context-dependent antiproliferative activity, but the association between mangiferin abundance and activity is inconsistent and cannot establish constituent-level causality. Purified mangiferin has inhibited growth or invasion in selected breast, lung, colorectal and ovarian cancer models, including several animal experiments. Reported mechanisms encompass apoptotic signalling, cell-cycle arrest, matrix metalloproteinase regulation, inflammatory transcriptional networks and altered mitochondrial metabolism. These pathways are not uniformly implicated, and target engagement often remains inferential. Combination studies reveal both sensitisation and the absence of benefit, depending on the cell model and anticancer drug. Human pharmacokinetic observations provide an important counterweight to laboratory efficacy claims: systemic concentrations after oral administration are far below many experimentally active concentrations, although formulation changes can improve relative exposure. No convincing clinical evidence of anticancer efficacy was established in the reviewed sources. The most defensible therapeutic prospect lies in development of chemically standardised, exposure-validated investigational products supported by mechanistic rescue experiments, comparative pharmacology and tumour-bearing safety studies rather than in immediate clinical use of mango-leaf preparations.