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

Mol Cancer Ther. 2006 Sep;5(9):2300-9. doi: 10.1158/1535-7163.MCT-06-0170.


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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

  • Animals
  • Antineoplastic Agents, Phytogenic / pharmacology
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Apoptosis Regulatory Proteins / biosynthesis
  • Apoptosis Regulatory Proteins / physiology*
  • Bcl-2-Like Protein 11
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Cell Cycle / drug effects
  • Cell Division / drug effects
  • Cell Growth Processes / drug effects
  • Cell Line, Tumor
  • Fatty Alcohols / isolation & purification
  • Fatty Alcohols / pharmacology*
  • G2 Phase / drug effects
  • Humans
  • Lactation
  • Mammary Glands, Animal / drug effects
  • Mammary Glands, Animal / pathology
  • Membrane Proteins / biosynthesis
  • Membrane Proteins / physiology*
  • Mice
  • Microtubules / drug effects
  • Microtubules / metabolism
  • Persea / chemistry*
  • Plant Leaves / chemistry
  • Proto-Oncogene Proteins / biosynthesis
  • Proto-Oncogene Proteins / physiology*
  • Proto-Oncogene Proteins c-bcl-2 / biosynthesis
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Transfection


  • 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