From teratogens to potential therapeutics: natural inhibitors of the Hedgehog signaling network come of age.
Steroidal alkaloids from Veratrum californicum (Durand) are known to exert teratogenic effects (e.g., cyclopia, holoprosencephaly) by blocking the Hedgehog (Hh) signaling pathway, which plays a considerable role in embryonic development and organogenesis. Most surprisingly, recent studies demonstrate that this complex signaling network is active even in the healthy adult organism, where it seems to control important aspects of basic metabolism and interorgan homeostasis. Abnormal activation of Hh signaling, however, can lead to the development of different tumors, psoriasis, and other diseases. This review provides an overview of how the principle teratogenic and hazardous constituent of Veratrum californicum, cyclopamine, interferes with Hh signaling and can potentially serve as a beneficial therapeutic for different tumors and psoriasis.
Hovhannisyan
Amalya
A
Institute of Biochemistry, Medical Faculty, University of Leipzig, Leipzig, Germany.
Matz
Madlen
M
Gebhardt
Rolf
R
D000328:Adult; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology / Q000627:therapeutic use; D005260:Female; D053823:Hedgehog Proteins / Q000037:antagonists & inhibitors* / Q000502:physiology; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000188:drug therapy*; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D011565:Psoriasis / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects*; D013723:Teratogens / Q000494:pharmacology; D014703:Veratrum / Q000737:chemistry*; D014704:Veratrum Alkaloids / Q000494:pharmacology / Q000627:therapeutic use*
D000972:Antineoplastic Agents, Phytogenic; D053823:Hedgehog Proteins; D010936:Plant Extracts; D013723:Teratogens; D014704:Veratrum Alkaloids; C000541:cyclopamine