Mangosteen (Garcinia mangostana L.)
Ayman EL-Meghawry EL-Kenawy, ... Hosam-Eldin Hussein Osman, in Nonvitamin and Nonmineral Nutritional Supplements, 2019
Anticancer Action of Mangosteen Compounds
The distinctive physical and chemical properties of xanthones show promise for dietary chemoprevention due to their putative health benefits and the protection they clearly provide (Shan et al., 2011).
It has long been advocated that many xanthones from this fruit including α-mangostin possess anticancer properties that could be used in prostate, breast, lung, colorectal, and cutaneous cancer by initiating and regulating cell death pathways, suppressing cancer cell propagation and spread, and arresting the cell cycle (Arcangeli et al., 2012; Li et al., 2013).
α-Mangostin in the human breast cancer cell line MDA–MB231 induced programmed cell death through the mitochondrial pathway and significantly elevated the ssDNA, caspase 3, 8, and 9 levels (Kurose et al., 2012).
α-Mangostin has a significant effect against head and neck squamous cell carcinoma (HNSCC) cell lines (Kaomongkolgit et al., 2011). α-Mangostin reduces cancer growth and spread to the lymph nodes via an immune-competent xenograft model of metastatic mammary cancer carrying a p53 mutation (Shibata et al., 2011).
Mangosteen extract containing α-mangostin and γ-mangostin completely suppresses the growth of HCT 116 colorectal carcinoma in vitro and in vivo by caspase-mediated apoptosis (Buelna-Chontal et al., 2011).
The antiapoptotic properties of xanthones in α-mangostin have been examined and documented as antimelanoma agents via caspase stimulation, which involves increasing 25-fold the activity of caspase-3 and caspase-9 and disrupting the mitochondrial cell cycle membrane when matched to untreated cells (Wang et al., 2011).
Xanthones from mangosteen extracts as natural chemopreventive agents: potential anticancer drugs
T Shan 1, Q Ma, K Guo, J Liu, W Li, F Wang, E Wu
Affiliations expand
PMID: 21902651 PMCID: PMC3237908 DOI: 10.2174/156652411797536679
Free PMC article
Abstract
Despite decades of research, the treatment and management of malignant tumors still remain a formidable challenge for public health. New strategies for cancer treatment are being developed, and one of the most promising treatment strategies involves the application of chemopreventive agents.
The search for novel and effective cancer chemopreventive agents has led to the identification of various naturally occurring compounds. Xanthones, from the pericarp, whole fruit, heartwood, and leaf of mangosteen (Garcinia mangostana Linn., GML), are known to possess a wide spectrum of pharmacologic properties, including antioxidant, anti- tumor, anti-allergic, anti-inflammatory, anti-bacterial, anti-fungal, and anti-viral activities.
The potential chemopreventive and chemotherapeutic activities of xanthones have been demonstrated in different stages of carcinogenesis (initiation, promotion, and progression) and are known to control cell division and growth, apoptosis, inflammation, and metastasis. Multiple lines of evidence from numerous in vitro and in vivo studies have confirmed that xanthones inhibit proliferation of a wide range of human tumor cell types by modulating various targets and signaling transduction pathways.
Here we provide a concise and comprehensive review of preclinical data and assess the observed anticancer effects of xanthones, supporting its remarkable potential as an anticancer agent.
Anti-Inflammatory Effects
It has been recognized that the components of the inflammatory signaling pathways are associated with carcinogenesis [44]. Mangosteen has been shown to exhibit substantial antiphlogistic activity. Shankaranarayan et al. reported that α-mangostin, 1-isomangostin and mangostin triacetate exhibited anti-inflammatory activity in a rat model [57].
Gopalakrishnan also demonstrated that α-mangostin inhibited systemic anaphylaxis and immunocyto-adherence in guinea pigs and rats [58]. Chairungsrilerd et al. showed that α- and γ-mangostins could inhibit the contractions of isolated thoracic rabbit aorta induced by histamine and serotonin, suggesting that these mangostin compounds are histaminergic and serotonergic receptor blocking agents [59]. Furthermore, α- and γ-mangostin suppressed the release of histamine from IgE-sensitized rat basophilic leukemia RBL-2H3 cells [60, 61], and the results from these studies indicate that the likely mechanism of xanthones mainly involves the suppression of the Syk/PLCγs/PKC pathway.
Induction of Cancer Cell Cycle Arrest
It is well known that the cell cycle is normally regulated by a number of proteins, including p53, p21waf, the cyclin-dependent kinases (cdks) and their activators, the cyclins.
The dysregulation of cell cycle machinery and checkpoint signaling pathways is a hallmark of malignant cells [73, 74]. Thus, modulation of cell cycle progression is one of the major strategies for both chemoprevention and chemotherapy. Treatment of mangosteen results in a direct inhibition of the proliferation and viability of various cancer cell types in vitro, as manifested by the significant arrest of cells at various phases of the cell cycle [23].
Matsumoto et al. demonstrated that the antiproliferative effects of four structurally similar prenylated xanthones, α-mangostin, β-mangostin, γ-mangostin, and methoxy- β-mangostin, were associated with cell cycle arrest mediated by modulation of the expression of cyclin A, B1, D1, E1, cdc2 or p27 in human colon cancer DLD-1 cells.
The exposure of α-mangostin and β-mangostin to DLD-1 cells resulted in G1 arrest, and treatment of γ-mangostin led to S arrest [42]. These findings provide a rational basis for the development of xanthones as agents for cancer prevention or for use in combination with anti-cancer drugs; however, further experiments are required to explore the precise molecular mechanisms underlying the observed induction of cell cycle arrest (Fig. 5).