Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells.

Carcinogenesis

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden.

Published: June 2010


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Article 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.

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http://dx.doi.org/10.1093/carcin/bgq084DOI Listing

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Extract from Asteraceae Brachylaena ramiflora induces apoptosis preferentially in mutant p53-expressing human tumor cells.

Carcinogenesis

June 2010

Department of Oncology-Pathology, Cancer Center Karolinska, Karolinska University Hospital, Karolinska Institutet, SE-171 76, Stockholm, Sweden.

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.

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Bioassay-guided fractionation of a CH(2)Cl(2)/MeOH extract of the small twigs of Brachylaena ramiflora var. ramiflora resulted in the isolation of the two new triterpene esters 1 and 2 and five known triterpenoids, alpha-amyrin palmitate (3), beta-amyrin palmitate (4), beta-amyrin acetate (5), lupeyl acetate (6), and lupeol (7). The structures of the two new compounds were established as kairatenyl palmitate (1) and hopenyl palmitate (2) on the basis of 1D and 2D NMR spectroscopic data interpretation and chemical conversions.

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