title: Cambogin is preferentially cytotoxic to cells expressing PDGFR.
abstract: Platelet-derived growth factor receptors (PDGFRs) have been implicated in a wide array of human malignancies, including medulloblastoma (MB), the most common brain tumor of childhood. Although significant progress in MB biology and therapeutics has been achieved during the past decades, MB remains a horrible challenge to the physicians and researchers. Therefore, novel inhibitors targeting PDGFR signaling pathway may offer great promise for the treatment of MB. In the present study, we investigated the cytotoxicity and mechanisms of cambogin in Daoy MB cells. Our results show that cambogin triggers significant S phase cell cycle arrest and apoptosis via down regulation of cyclin A and E, and activation of caspases. More importantly, further mechanistic studies demonstrated that cambogin inhibits PDGFR signaling in Daoy and genetically defined mouse embryo fibroblast (MEF) cell lines. These results suggest that cambogin is preferentially cytotoxic to cells expressing PDGFR. Our findings may provide a novel approach by targeting PDGFR signaling against MB.
authors.affiliation: Institute of Medicinal Plant Development, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China. ze_tian@dfci.harvard.edu
authors.forename: Ze
authors.initials: Z
authors.lastname: Tian
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Fengfei
authors.initials: F
authors.lastname: Wang
authors.forename: Peigen
authors.initials: P
authors.lastname: Xiao
authors.forename: Junshan
authors.initials: J
authors.lastname: Yang
authors.forename: Hetian
authors.initials: H
authors.lastname: Lei
authors.forename: Andrius
authors.initials: A
authors.lastname: Kazlauskas
authors.forename: Isaac S
authors.initials: IS
authors.lastname: Kohane
authors.forename: Erxi
authors.initials: E
authors.lastname: Wu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D019925:Cyclin A / Q000378:metabolism; D019927:Cyclin E / Q000378:metabolism; D006801:Humans; D008527:Medulloblastoma / Q000378:metabolism / Q000473:pathology; D051379:Mice; D018345:Mice, Knockout; D015394:Molecular Structure; D010936:Plant Extracts / Q000737:chemistry / Q000633:toxicity; D020796:Receptor, Platelet-Derived Growth Factor alpha / Q000235:genetics / Q000378:metabolism*; D020797:Receptor, Platelet-Derived Growth Factor beta / Q000235:genetics / Q000378:metabolism*; D016196:S Phase / Q000187:drug effects*; D015398:Signal Transduction / Q000187:drug effects; D013729:Terpenes / Q000737:chemistry / Q000633:toxicity*
chemical_list: D019925:Cyclin A; D019927:Cyclin E; D010936:Plant Extracts; D013729:Terpenes; D020796:Receptor, Platelet-Derived Growth Factor alpha; D020797:Receptor, Platelet-Derived Growth Factor beta; C054597:garcinol