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Research Articles: Therapeutics

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

¹ Cancer Research Program, Garvan Institute of Medical Research, St. Vincent's Hospital, Darlinghurst, New South Wales, Australia; ² St. Vincent's Clinical School, Faculty of Medicine, University of New South Wales, Sydney, New South Wales, Australia; ³ National Research Centre for Environmental Toxicology, University of Queensland, Brisbane, Queensland, Australia; ⁴ Research School of Chemistry, Australian National University, Canberra, Australian Capital Territory, Australia; and ⁵ Children's Cancer Institute Australia for Medical Research, Randwick, New South Wales, Australia

Requests for reprints: Alison J. Butt, Cancer Research Program, Garvan Institute of Medical Research, 384 Victoria Street, Darlinghurst, New South Vales 2010, Australia. Phone: 612-9295-8327; Fax: 612-9295-8321. E-mail: abutt{at}garvan.org.au

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. [Mol Cancer Ther 2006;5(9):2300–9]

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

⁶ A.A. Seawright, personal communication.

Received 3/29/06; revised 6/25/06; accepted 7/12/06.

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