Cyclopamine and Hedgehog Signaling: Chemistry, Biology, Medical Perspectives

Abstract

When Odysseus left the devastated city of Troy after ten years of siege he could not foresee the perils he still had to face. The encounter with the cyclops, a giant with only one eye placed in the middle of its forehead, was doubtlessly one of the creepiest and most dangerous of his adventures. In the end, Odysseus could only escape with the help of a sheep. Whether Homers cyclops was inspired by the observation of terribly malformed neonates remains speculative. However, when sheep herders in Idaho in the middle of the 20th century faced an increasing number of cyclops-like sheep in their herds, a unique cascade of chemical, biological, and medicinal discoveries was initiated. This Minireview tells this story and shows its impact on modern biomedical research.

Gender-Dependent Pharmacokinetics of Veratramine in Rats: In Vivo and In Vitro Evidence

“…Due to their potent biological activities, steroidal alkaloids have been investigated for their pharmacokinetic and pharmacodynamic characteristics (30)(31)(32)(33). However, up to now, few studies evaluated the pharmacokinetic profile of veratramine and explored its potential gender-associated pharmacokinetics.…”

“…Blood samples (300 μL) were collected into heparinized tubes via a jugular vein catheter at 5,10,20,30,60,90,120,240,360,480,720,1440,2160, and 2880 min after oral administration, with a 300-μL saline given via the indwelling catheter immediately after each blood collection. The plasma was obtained by centrifugation of the collected blood at 4000×g for 5 min.…”

Multifunctional Nanoparticles for Prostate Cancer Therapy

“…Cyclopamine is a steroidal alkaloid obtained from ground roots and rhizomes of Veratrum californicum belonging to the family Melanthiaceae. This plant also known as California false hellebore (8). Cyclopamine is an inhibitor of the Sonic Hedgehog pathway responsible for the growth and proliferation of cancer stem cells.…”

Toxicogenomics for transcription factor-governed molecular pathways: moving on to roles beyond classification and prediction

“…Most other pathways that signal through binding to surface receptors also coordinate patterns of gene expression to influence cellular phenotypic consequences. In contemporary toxicology, we have less emphasis on toxicants that preferentially target surface receptors, such as cyclopamine and hedgehog pathway signaling (Heretsch et al 2010) or belladonna alkaloids acting through acetylcholine neurotransmission at G protein-coupled receptors. In vitro testing of the toxicogenomic properties and structure of these various pathwaysnuclear receptors, stress and inflammatory responses, and a variety of surface receptor signaling-will continue to elaborate detailed pathway information to empower broader use of in vitro assays of transcription factor-governed assays in risk assessment.…”