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A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells

2006; American Association for Cancer Research; Volume: 5; Issue: 9 Linguagem: Inglês

10.1158/1535-7163.mct-06-0170

1538-8514

Alison J. Butt, Caroline Roberts, Alan A. Seawright, Peter B. Oelrichs, John K. MacLeod, Tracy Y.E. Liaw, Maria Kavallaris, Tiffany J. Somers‐Edgar, Gillian M. Lehrbach, Colin Watts, Robert L. Sutherland,

Cancer therapeutics and mechanisms

Abstract Phytochemicals have provided an abundant and effective source of therapeutics for the treatment of cancer. Here we describe the characterization of a novel plant toxin, persin, with in vivo activity in the mammary gland and a p53-, estrogen receptor–, and Bcl-2-independent mode of action. Persin was previously identified from avocado leaves as the toxic principle responsible for mammary gland–specific necrosis and apoptosis in lactating livestock. Here we used a lactating mouse model to confirm that persin has a similar cytotoxicity for the lactating mammary epithelium. Further in vitro studies in a panel of human breast cancer cell lines show that persin selectively induces a G2-M cell cycle arrest and caspase-dependent apoptosis in sensitive cells. The latter is dependent on expression of the BH3-only protein Bim. Bim is a sensor of cytoskeletal integrity, and there is evidence that persin acts as a microtubule-stabilizing agent. Due to the unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers. [Mol Cancer Ther 2006;5(9):2300–9]