title: The effect of gartanin, a naturally occurring xanthone in mangosteen juice, on the mTOR pathway, autophagy, apoptosis, and the growth of human urinary bladder cancer cell lines.
abstract: Garcinia mangostana, often referred to as mangosteen, is a fruit grown in Southeast Asia and has been used for centuries as a local beverage and natural medicine. Its bioactive compounds, xanthones (i.e., gartanin, α-mangostin, etc), have reported effects on ailments ranging from skin infections and inflammation to urinary tract infections. We demonstrate that mangosteen xanthones (i.e., gartanin and α-mangostin) at pharmacologically achievable concentrations inhibit the growth of cancer cell lines from different stages of human urinary bladder cancer. The growth inhibitory effects of gartanin in mouse embryonic fibroblasts are at least in part dependent on the existence of p53 or TSC1. Indeed, further studies have shown that gartanin treatment of bladder cancer cell lines T24 and RT4 resulted in a marked suppression of p70S6 and 4E-BP1 expression and induction of autophagy, suggesting the inhibition of the mTOR pathway. In addition, gartanin downregulated the expression of Bcl-2 and activated the p53 pathway leading to apoptosis induction. Together, these results suggested that gartanin is a multiple targeting agent that is suitable for further study into its chemopreventive properties for human urinary bladder cancer.
authors.affiliation: Department of Urology, University of California, Irvine, Orange, California 92868, USA.
authors.forename: Zhongbo
authors.initials: Z
authors.lastname: Liu
authors.forename: Mitchell
authors.initials: M
authors.lastname: Antalek
authors.forename: Linda
authors.initials: L
authors.lastname: Nguyen
authors.forename: Xuesen
authors.initials: X
authors.lastname: Li
authors.forename: Xuejiao
authors.initials: X
authors.lastname: Tian
authors.forename: Amy
authors.initials: A
authors.lastname: Le
authors.forename: Xiaolin
authors.initials: X
authors.lastname: Zi
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000235:genetics / Q000378:metabolism; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism; D001343:Autophagy / Q000187:drug effects*; D001628:Beverages / Q000032:analysis*; D018797:Cell Cycle Proteins; D045744:Cell Line, Tumor; D015536:Down-Regulation; D005638:Fruit / Q000737:chemistry; D029762:Garcinia mangostana / Q000737:chemistry*; D006801:Humans; D051379:Mice; D008856:Microscopy, Fluorescence; D010750:Phosphoproteins / Q000235:genetics / Q000378:metabolism; D011518:Proto-Oncogene Proteins / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics / Q000378:metabolism*; D000077004:Tuberous Sclerosis Complex 1 Protein; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation; D001749:Urinary Bladder Neoplasms / Q000473:pathology; D044004:Xanthones / Q000494:pharmacology*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; C438378:BBC3 protein, human; D018797:Cell Cycle Proteins; C087000:EIF4EBP1 protein, human; D010750:Phosphoproteins; D011518:Proto-Oncogene Proteins; C495901:TP53 protein, human; C090468:TP53BP2 protein, human; C000624650:TSC1 protein, human; C000624651:Tsc1 protein, mouse; D000077004:Tuberous Sclerosis Complex 1 Protein; D016159:Tumor Suppressor Protein p53; D025521:Tumor Suppressor Proteins; D044004:Xanthones; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C021053:mangostin