title: Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells.
abstract: The p53 tumor suppressor gene is inactivated by point mutation in a large fraction of human tumors, allowing evasion of apoptosis and tumor progression. p53 mutation is often associated with increased resistance to therapy. Pharmacological reactivation of mutant p53 is an attractive therapeutic strategy. We previously identified p53 reactivation and induction of massive apoptosis, a low-molecular weight compound that suppresses the growth of cancer cells in a mutant p53-dependent manner. Here, we report the identification and characterization of an extract from the terrestrial plant Brachylaena ramiflora (Asteraceae) that preferentially induces apoptosis in human tumor cells expressing mutant p53. Further analysis of this extract and identification of active compounds may provide novel structural scaffolds for the development of mutant p53-targeting anticancer drugs.
authors.affiliation: Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
authors.forename: Masoud
authors.initials: M
authors.lastname: Karimi
authors.forename: Francesca
authors.initials: F
authors.lastname: Conserva
authors.forename: Salah
authors.initials: S
authors.lastname: Mahmoudi
authors.forename: Jan
authors.initials: J
authors.lastname: Bergman
authors.forename: Klas G
authors.initials: KG
authors.lastname: Wiman
authors.forename: Vladimir J N
authors.initials: VJ
authors.lastname: Bykov
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D019659:Asteraceae / Q000737:chemistry*; D020169:Caspases / Q000378:metabolism; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D005434:Flow Cytometry; D006801:Humans; D009154:Mutation; D010936:Plant Extracts / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016159:Tumor Suppressor Protein p53 / Q000235:genetics*
chemical_list: D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D020169:Caspases