Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells.
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.
Karimi
Masoud
M
Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden.
Conserva
Francesca
F
Mahmoudi
Salah
S
Bergman
Jan
J
Wiman
Klas G
KG
Bykov
Vladimir J N
VJ
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*
D010936:Plant Extracts; D017382:Reactive Oxygen Species; D016159:Tumor Suppressor Protein p53; D020169:Caspases