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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.

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.
AuthorsAlison 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
JournalMolecular cancer therapeutics (Mol Cancer Ther) Vol. 5 Issue 9 Pg. 2300-9 (Sep 2006) ISSN: 1535-7163 [Print] United States
PMID16985064 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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
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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