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

Butt, Alison J., Roberts, Caroline G., Seavvright, Alan A., Oelrichs, Peter B., MacLeod, John K., Liaw, Tracy Y.E., Kavallaris, Maria, Somers-Edgar, Tiffany J., Lehrbach, Gillian M., Watts, Colin K. and Sutherland, Robert L. (2006) A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells. Molecular Cancer Therapeutics, 5 9: 2300-2309.


Author Butt, Alison J.
Roberts, Caroline G.
Seavvright, Alan A.
Oelrichs, Peter B.
MacLeod, John K.
Liaw, Tracy Y.E.
Kavallaris, Maria
Somers-Edgar, Tiffany J.
Lehrbach, Gillian M.
Watts, Colin K.
Sutherland, Robert L.
Title A novel plant toxin, persin, with in vivo activity in the mammary gland, induces Bim-dependent apoptosis in human breast cancer cells
Journal name Molecular Cancer Therapeutics  (ERA 2012 Listed)    (ERA 2010 Rank A)   Check publisher's open access policy
Publication date 2006
Sub-type Article
DOI 10.1158/1535-7163.MCT-06-0170
Volume number 5
Issue number 9
ISSN 1535-7163
Start page 2300
End page 2309
Total pages 10
Editor D. D. Von Hoff
Place of publication Philadelphia
Publisher American Association for Cancer Research
Collection year 2006
Language eng
Subject C1
321299 Public Health and Health Services not elsewhere classified
730299 Public health not elsewhere classified
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 G(2)-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 unique structure of the compound, persin could represent a novel class of microtubule-targeting agent with potential specificity for breast cancers.
Keyword Oncology
Growth-factor
Bcl-2 Family
Bax
Resistance
Agents
Member
Roles
Drugs
Lines
Acid
Q-Index Code C1

 
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