title: New targets for the antitumor activity of gambogic acid in hematologic malignancies.
abstract: Gambogic acid (GA) is the main active ingredient of gamboge, a brownish to orange dry resin secreted from Garcinia hanburyi, a plant that is widely distributed in nature. Recent in vitro and in vivo studies have demonstrated that GA exerts potent antitumor effects against solid tumors of various derivations, and its antitumor mechanisms have been thoroughly investigated. On the other hand, normal cells remain relatively resistant to GA, indicating a therapeutic window. GA is currently in clinical trials in China. Over the last decade, our laboratory demonstrates that GA exhibits potent anticancer activities against hematological malignancies. This review focuses on the new mechanisms through which GA inhibits proliferation and induces apoptosis in malignant hematological cells. These include the regulation of expression and intracellular positioning of nucleoporin and nucleophosmin; downregulation of steroid receptor coactivator-3 (SRC-3) and its downstream proteins; upregulation of death inducer-obliterator (DIO-1); downregulation of HERG potassium channel; as well as induction of reactive oxygen species (ROS) accumulation.
authors.affiliation: Department of Hematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Li-jing
authors.initials: LJ
authors.lastname: Yang
authors.forename: Yan
authors.initials: Y
authors.lastname: Chen
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use; D004268:DNA-Binding Proteins / Q000378:metabolism; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels / Q000378:metabolism; D029760:Garcinia / Q000737:chemistry*; D019337:Hematologic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D028861:Nuclear Pore Complex Proteins / Q000378:metabolism; D009687:Nuclear Proteins / Q000378:metabolism; D056921:Nuclear Receptor Coactivator 3 / Q000378:metabolism; D000090243:Nucleophosmin; D017382:Reactive Oxygen Species / Q000378:metabolism; D044004:Xanthones / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use
chemical_list: D000972:Antineoplastic Agents, Phytogenic; C518584:DIDO1 protein, human; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C000606913:KCNH2 protein, human; C000716967:NPM1 protein, human; D028861:Nuclear Pore Complex Proteins; D009687:Nuclear Proteins; D017382:Reactive Oxygen Species; D044004:Xanthones; D000090243:Nucleophosmin; C052659:gambogic acid; C538866:NCOA3 protein, human; D056921:Nuclear Receptor Coactivator 3