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.
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Authors | Alison J Butt, Caroline G Roberts, Alan A Seawright, Peter B Oelrichs, John K Macleod, Tracy Y E Liaw, Maria Kavallaris, Tiffany J Somers-Edgar, Gillian M Lehrbach, Colin K Watts, Robert L Sutherland |
Journal | Molecular cancer therapeutics
(Mol Cancer Ther)
Vol. 5
Issue 9
Pg. 2300-9
(Sep 2006)
ISSN: 1535-7163 [Print] United States |
PMID | 16985064
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Antineoplastic Agents, Phytogenic
- Apoptosis Regulatory Proteins
- BCL2L11 protein, human
- Bcl-2-Like Protein 11
- Bcl2l11 protein, mouse
- Fatty Alcohols
- Membrane Proteins
- Proto-Oncogene Proteins
- Proto-Oncogene Proteins c-bcl-2
- persin
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Topics |
- Animals
- Antineoplastic Agents, Phytogenic
(pharmacology)
- Apoptosis
(drug effects, physiology)
- Apoptosis Regulatory Proteins
(biosynthesis, physiology)
- Bcl-2-Like Protein 11
- Breast Neoplasms
(drug therapy, genetics, pathology)
- Cell Cycle
(drug effects)
- Cell Division
(drug effects)
- Cell Growth Processes
(drug effects)
- Cell Line, Tumor
- Fatty Alcohols
(isolation & purification, pharmacology)
- G2 Phase
(drug effects)
- Humans
- Lactation
- Mammary Glands, Animal
(drug effects, pathology)
- Membrane Proteins
(biosynthesis, physiology)
- Mice
- Microtubules
(drug effects, metabolism)
- Persea
(chemistry)
- Plant Leaves
(chemistry)
- Proto-Oncogene Proteins
(biosynthesis, physiology)
- Proto-Oncogene Proteins c-bcl-2
(biosynthesis, genetics)
- Transfection
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