Current Study of Alpha-Mangostin in Breast Cancer Therapy: Antioxidant Mechanisms and Redox Modulation from In Silico to In Vivo Studies.

Breast cancer remains a major disease burden and a leading cause of cancer-related morbidity and mortality among women, while current therapies are often limited by toxicity, drug resistance, and recurrence. α-Mangostin (AM), a prenylated xanthone derived from Garcinia mangostana L., has attracted considerable interest because of its antioxidant, redox-modulating, and anticancer properties, which may contribute to improved health outcomes and patient well-being. This study systematically reviewed the therapeutic potential of AM against breast cancer based on evidence from in silico, in vitro, and in vivo studies focusing on biomedical and pharmaceutical applications. Relevant articles were retrieved from the Scopus and PubMed databases using predefined keywords and selection criteria. Eligible studies were extracted, categorized, and analyzed using Microsoft Word and EndNote to assess the pharmacological actions, target interactions, delivery systems, and therapeutic outcomes associated with AM, while the quality of animal studies was assessed using the ARRIVE guidelines. Twenty-nine studies met the inclusion criteria. Computational studies demonstrated favorable AM interactions with ERα, STAT3, RXRα, CXCR4, AKT1, CTNNB1, and HSP90AA1. In vitro studies showed that AM inhibited cancer cell viability, induced apoptosis and autophagy, modulated reactive oxygen species, and suppressed metastatic and immune-evasion markers. Furthermore, nano-formulations, radiolabeled derivatives, and combination approaches improved bioavailability, tumor targeting, and efficacy. In vivo studies reported inhibition of tumor-growth and metastasis, improved pharmacokinetic profiles, and prolonged survival. However, no clinical trials evaluating AM in breast cancer patients have been reported to date. Overall, AM represents a promising preclinical candidate for breast cancer treatment. Nevertheless, standardized pharmacokinetic, toxicological, and efficacy studies, followed by well-designed clinical trials, are essential to facilitate its translation into clinical practice.