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Cyclopamine: From Cyclops Lambs to Cancer Treatment

Author:
Stephen T. Lee, Kevin D. Welch, Kip E. Panter, Dale R. Gardner, Massoud Garrossian, Cheng-Wei Tom Chang
Source:
Journal of agricultural and food chemistry 2014 v.62 no.30 pp. 7355-7362
ISSN:
0021-8561
Subject:
Veratrum californicum, congenital abnormalities, cyclopamine, embryogenesis, grazing, lambs, mountains, neoplasms, progeny, signal transduction, Western United States
Abstract:
In the late 1960s, the steroidal alkaloid cyclopamine was isolated from the plant Veratrum californicum and identified as the teratogen responsible for craniofacial birth defects including cyclops in the offspring of sheep grazing on mountain ranges in the western United States. Cyclopamine was found to inhibit the hedgehog (Hh) signaling pathway, which plays a critical role in embryonic development. More recently, aberrant Hh signaling has been implicated in several types of cancer. Thus, inhibitors of the Hh signaling pathway, including cyclopamine derivatives, have been targeted as potential treatments for certain cancers and other diseases associated with the Hh signaling pathway. A brief history of cyclopamine and cyclopamine derivatives investigated for the treatment of cancer is presented.
Agid:
4791518
Handle:
10113/4791518