title: Cyclopamine: from cyclops lambs to cancer treatment.
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.
authors.affiliation: Poisonous Plant Research Laboratory, Agricultural Research Service, U.S. Department of Agriculture, 1150 East 1400 North, Logan, Utah 84341, United States.
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Lee
authors.forename: Kevin D
authors.initials: KD
authors.lastname: Welch
authors.forename: Kip E
authors.initials: KE
authors.lastname: Panter
authors.forename: Dale R
authors.initials: DR
authors.lastname: Gardner
authors.forename: Massoud
authors.initials: M
authors.lastname: Garrossian
authors.forename: Cheng-Wei Tom
authors.initials: CW
authors.lastname: Chang
mesh_terms: D000821:Animal Feed / Q000032:analysis / Q000633:toxicity; D000818:Animals; D053823:Hedgehog Proteins / Q000235:genetics / Q000378:metabolism; D016142:Holoprosencephaly / Q000139:chemically induced / Q000473:pathology; D006801:Humans; D009154:Mutation; D009369:Neoplasms / Q000188:drug therapy*; D010936:Plant Extracts / Q000737:chemistry / Q000494:pharmacology*; D034561:Sheep, Domestic / Q000002:abnormalities*; D015398:Signal Transduction; D013723:Teratogens / Q000633:toxicity; D014703:Veratrum / Q000737:chemistry*; D014704:Veratrum Alkaloids / Q000737:chemistry / Q000633:toxicity*
chemical_list: D053823:Hedgehog Proteins; D010936:Plant Extracts; D013723:Teratogens; D014704:Veratrum Alkaloids; C000541:cyclopamine