A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
Date
2006
Authors
Butt, Alison J
Roberts, Caroline G
Seawright, Alan A
Oelrichs, Peter B
MacLeod, John
Liaw, Tracy Y E
Kavallaris, Maria
Somers-Edgar, Tiffany J
Lehrbach, Gillian M
Watts, Colin K
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Volume Title
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American Association for Cancer Research
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 cancer.
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Keywords: BIM protein; caspase; cytotoxic agent; estrogen receptor; persin; plant toxin; protein bcl 2; protein p53; unclassified drug; apoptosis; article; avocado; breast cancer; breast epithelium; cancer cell; cell cycle arrest; cell cycle G2 phase; cell cycle M
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Molecular Cancer Therapeutics
Type
Journal article
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2037-12-31
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