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

Abstract

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: Mangifera indica; breast cancer; mangiferin; mango; molecular mechanism; natural products; women’s health.

Figure 1

An overview of effects of M. indica extracts and their phytochemicals against breast cancer. Extracts of various M. indica parts (bark, kernel, leaves, peel and pulp) have been used to treat a variety of medical problems including breast cancer; as these plant parts contain varying types and amounts of polyphenols, some of which possess anti-proliferative and pro-apoptotic activities. According to phytochemical profile analysis, the anti-cancer activity of M. indica extracts is mostly attributable to the presence of polyphenolic compounds such as mangiferin, gallotannins, gallic acid, pyrogallol, methyl gallate and quercetin.

Figure 2

Activation of oxidative stress-induced cell death and antioxidant activity as the anti-cancer mechanisms of M. indica extracts and phytochemicals.

Figure 3

Suppression of PI3K/AKT/mTOR pathway by M. indica extracts and phytochemicals via reduction of pathway components’ mRNA, total protein and phosphorylated protein levels.

Figure 4

Inhibition of classical and parallel NFκB activation pathways by M. indica extracts and phytochemicals.

Figure 5

Inactivation of β-catenin pathway by mangiferin.

Figure 6

Inhibition of Rac1/WAVE2 signalling pathway by mangiferin. Arp2/3, activating the actin-related protein 2/3; Cdc42, cell division control protein 42 homolog; GEF, guanine nucleotide exchange factor; Rac1, Ras-related C3 botulinum toxin substrate 1; WASP, Wiskott–Aldrich syndrome protein; WAVE, WASP-family verprolin-homologous protein.

Figure 7

Activation of AMPK signalling pathway by M. indica extracts and phytochemicals.

Figure 8

Fabrication of smart nanofiber matrices for breast cancer therapy. Polyphenolic compounds (PLP) from M. indica have been studied extensively as anti-inflammatory and anti-cancer agents. In the proposed future study, M. indica PLP will be cross-linked to silk fibroin (cocoon) nanofibers before being conjugated with PNIPAAm-PEG-Tat to yield PNIPAAm-PLP-Tat, which can then be released in a thermal responsive burst at breast tumor tissues. The use of cell-penetrating peptide (Tat) permits targeted intracellular transport of PLP into breast cancer cells.