Mangifera indica (Mango): A Promising Medicinal Plant for Breast Cancer Therapy and Understanding Its Potential Mechanisms of Action

Kah Min Yap,1 Mahendran Sekar,1 Lay Jing Seow,1 Siew Hua Gan,2 Srinivasa Reddy Bonam,3 Nur Najihah Izzati Mat Rani,4 Pei Teng Lum,1 Vetriselvan Subramaniyan,5 Yuan Seng Wu,5 Neeraj Kumar Fuloria,6 Shivkanya Fuloria6 1Department of Pharmaceutical Chemistry, Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 2School of Pharmacy, Monash University Malaysia, Bandar Sunway, 47500, Selangor Darul Ehsan, Malaysia; 3Institut National de la Santé et de la Recherche Médicale; Centre de Recherche des Cordeliers, Equipe-Immunopathologie et Immunointervention Thérapeutique, Sorbonne Université, Université de Paris, Paris, France; 4Faculty of Pharmacy and Health Sciences, Universiti Kuala Lumpur Royal College of Medicine Perak, Ipoh, 30450, Perak, Malaysia; 5Faculty of Medicine, Bioscience and Nursing, MAHSA University, Selangor, 42610, Malaysia; 6Faculty of Pharmacy, AIMST University, Kedah, 08100, MalaysiaCorrespondence: Mahendran Sekar Tel +6016 – 3346653Fax +605 – 2536634Email mahendransekar@unikl.edu.myAbstract: Globally, breast cancer is the most common cancer type and is one of the most significant causes of deaths in women. To date, multiple clinical interventions have been applied, including surgical resection, radiotherapy, endocrine therapy, targeted therapy and chemotherapy. However, 1) the lack of therapeutic options for metastatic breast cancer, 2) resistance to drug therapy and 3) the lack of more selective therapy for triple-negative breast cancer are some of the major challenges in tackling breast cancer. Given the safe nature of natural products, numerous studies have focused on their anti-cancer potentials. Mangifera indica, commonly known as mango, represents one of the most extensively investigated natural sources. In this review, we provide a comprehensive overview of M. indica extracts (bark, kernel, leaves, peel and pulp) and phytochemicals (mangiferin, norathyriol, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin) reported for in vitro and in vivo anti-breast cancer activities and their underlying mechanisms based on relevant literature from several scientific databases, including PubMed, Scopus and Google Scholar till date. Overall, the in vitro findings suggest that M. indica extracts and/or phytochemicals inhibit breast cancer cell growth, proliferation, migration and invasion as well as trigger apoptosis and cell cycle arrest. In vivo results demonstrated that there was a reduction in breast tumor xenograft growth. Several potential mechanisms underlying the anti-breast cancer activities have been reported, which include modulation of oxidative status, receptors, signalling pathways, miRNA expression, enzymes and cell cycle regulators. To further explore this medicinal plant against breast cancer, future research directions are addressed. The outcomes of the review revealed that M. indica extracts and their phytochemicals may have potential benefits in the management of breast cancer in women. However, to validate its utility in the creation of innovative and potent therapeutic agents to treat breast cancer, more dedicated research, especially clinical studies are needed to explore the anti-breast cancer potentials of M. indica extracts and their phytochemicals.Keywords: mango, Mangifera indica, mangiferin, breast cancer, molecular mechanism, natural products, women’s health