Article

α-Mangostin, a xanthone from mangosteen fruit, promotes cell cycle arrest in prostate cancer and decreases xenograft tumor growth.

Department of Pharmacy Practice, University of Illinois at Chicago College of Pharmacy, 833 South Wood Street, Chicago, IL 60612-7230, USA.
Carcinogenesis (Impact Factor: 5.27). 12/2011; 33(2):413-9. DOI: 10.1093/carcin/bgr291
Source: PubMed

ABSTRACT There is a need to characterize promising dietary agents for chemoprevention and therapy of prostate cancer (PCa). We examined the anticancer effect of α-mangostin, derived from the mangosteen fruit, in human PCa cells and its role in targeting cell cycle-related proteins involved in prostate carcinogenesis. Using an 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay, we found that α-mangostin significantly decreases PCa cell viability in a dose-dependent manner. Further analysis using flow cytometry identified cell cycle arrest along with apoptosis. To establish a more precise mechanism of action, we performed a cell free biochemical kinase assay against multiple cyclins/cyclin-dependent kinases (CDKs) involved in cell cycle progression; the most significant inhibition in the cell free-based assays was CDK4, a critical component of the G1 phase. Through molecular modeling, we evaluated α-mangostin against the adenosine triphosphate-binding pocket of CDK4 and propose three possible orientations that may result in CDK4 inhibition. We then performed an in vivo animal study to evaluate the ability of α-mangostin to suppress tumor growth. Athymic nude mice were implanted with 22Rv1 cells and treated with vehicle or α-mangostin (100 mg/kg) by oral gavage. At the conclusion of the study, mice in the control cohort had a tumor volume of 1190 mm(3), while the treatment group had a tumor volume of 410 mm(3) (P < 0.01). The ability of α-mangostin to inhibit PCa in vitro and in vivo suggests α-mangostin may be a novel agent for the management of PCa.

Download full-text

Full-text

Available from: Imtiaz A Siddiqui, Jun 23, 2015
1 Follower
 · 
279 Views
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Ulcerative colitis (UC) is a chronic inflammatory disease of the colon. α-Mangostin (α-MG), the most abundant xanthone in mangosteen fruit, exerts anti-inflammatory and antibacterial activities in vitro. We evaluated the impact of dietary α-MG on murine experimental colitis and on the gut microbiota of healthy mice. Colitis was induced in C57BL/6J mice by administration of dextran sulfate sodium (DSS). Mice were fed control diet or diet with α-MG (0.1%). α-MG exacerbated the pathology of DSS-induced colitis. Mice fed diet with α-MG had greater colonic inflammation and injury, as well as greater infiltration of CD3(+) and F4/80(+) cells, and colonic myeloperoxidase, than controls. Serum levels of granulocyte colony-stimulating factor, IL-6, and serum amyloid A were also greater in α-MG-fed animals than in controls. The colonic and cecal microbiota of healthy mice fed α-MG but no DSS shifted to an increased abundance of Proteobacteria and decreased abundance of Firmicutes and Bacteroidetes, a profile similar to that found in human UC. α-MG exacerbated colonic pathology during DSS-induced colitis. These effects may be associated with an induction of intestinal dysbiosis by α-MG. Our results suggest that the use of α-MG-containing supplements by patients with UC may have unintentional risk.
    Molecular Nutrition & Food Research 06/2014; 58(6). DOI:10.1002/mnfr.201300771 · 4.91 Impact Factor
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: α -Mangostin, a natural product isolated from the pericarp of the mangosteen fruit, has been shown to inhibit the growth of tumor cells in various types of cancers. However, the underlying molecular mechanisms are largely unclear. Here, we report that α -mangostin suppressed the viability and epithelial-mesenchymal transition (EMT) of pancreatic cancer cells through inhibition of the PI3K/Akt pathway. Treatment of pancreatic cancer BxPc-3 and Panc-1 cells with α -mangostin resulted in loss of cell viability, accompanied by enhanced cell apoptosis, cell cycle arrest at G1 phase, and decrease of cyclin-D1. Moreover, Transwell and Matrigel invasion assays showed that α -mangostin significantly reduced the migration and invasion of pancreatic cancer cells. Consistent with these results, α -mangostin decreased the expression of MMP-2, MMP-9, N-cadherin, and vimentin and increased the expression of E-cadherin. Furthermore, we found that α -mangostin suppressed the activity of the PI3K/Akt pathway in pancreatic cancer cells as demonstrated by the reduction of the Akt phosphorylation by α -mangostin. Finally, α -mangostin significantly inhibited the growth of BxPc-3 tumor mouse xenografts. Our results suggest that α -mangostin may be potentially used as a novel adjuvant therapy or complementary alternative medicine for the management of pancreatic cancers.
    04/2014; 2014:546353. DOI:10.1155/2014/546353
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Beverages and supplements prepared from mangosteen fruit are claimed to support gut health and immunity, despite the absence of supporting evidence from clinical trials. We recently reported that α-mangostin (α-MG), the most abundant xanthone in mangosteen fruit, altered the intestinal microbiome, promoted dysbiosis, and exacerbated colitis in C57BL/6J mice. The objective of this study was to determine whether induction of dysbiosis by dietary α-MG is limited to the C57BL/6J strain or represents a more generic response to chronic intake of the xanthone on the gut microbiota of mice. C3H, Balb/c, Nude FoxN1nu, and C57BL/6J mice, each demonstrating unique microbiomes, were fed standard diet or diet containing 0.1% α-MG for four weeks. Dietary α-MG significantly altered the cecal and colonic microbiota in all four strains of mice, promoting a reduction in generally assumed beneficial bacterial groups while increasing the abundance of pathogenic bacteria. Consumption of α-MG was associated with reduced abundance of Firmicutes and increased abundance of Proteobacteria. The abundance of Lachnospiraceae, Ruminococcaceae, and Lactobacillaceae was reduced in α-MG-fed mice, while that of Enterobacteriaceae and Enterococcaceae was increased. Dietary α-MG also was associated with increased proliferation of colonic epithelial cells, infiltration of immune cells, infiltration of immune cells and increased fluid content in stool. These results suggest that ingestion of pharmacologic doses of xanthones in mangosteen-containing supplements may adversely alter the gut microbiota and should be used with caution.
    Nutrients 02/2015; 7(2):764-84. DOI:10.3390/nu7020764 · 3.15 Impact Factor