aka: corn lily false hellebore skunk cabbage family liliaceae native to mountain meadows in the...
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Veratrum californicum
AKA: Corn lily False hellebore Skunk cabbage
Family Liliaceae Native to mountain
meadows in the Sierra Nevadas and the Rockies
Medicinal Uses
Used by native Americans to treat wounds
Contraceptive
Root is an analgesic and disinfectant
Also used to treat VD
Sheep herds were plagued by unexplained birth defects
Intensive study by the USDA isolated cyclopamine as the causative agent
But what about cells that have already differentiated?
Required for tissue maintenance and regeneration
T-cell activation Can act as a
mitogen Tissue dependent
Smoothened is a GPCR, no wonder your cells died!
GPCRs (G Protein Coupled Receptor) are responsible for a multitude of signal cascades :1. Adenylate cyclase/cAMP pathway
Activates PKA, which activates ion channels
2. Phospholipase C pathway Secretion and translocation of proteins from the
ER
3. IP3 pathway: Releases Ca+ from ER activating
4. Ca+/Calmodulin pathway5. Glycogen pathway (via Adenylate cyclase)
Don’t worry, I’m a doctor!
Phase I clinical trials underway of a derivate
GDC-0449 (Genentech in collaboration with Curis)
Preliminary results were promising Side effects: loss of hair, weight loss,
otherwise mild toxicity reported Already being billed as “hav[ing] the
potential to become a blockbuster drug…for treating cancers.” (Wong, 2009)
But what type of cancer does it treat?
Glioblastoma multiforme (brain tumor) 2-3 cases per 100K Most often terminal Median survival = 15 months
(conventional chemotherapy) Without treatment = 4.5 months
(World Heath Organization)
Why the comparison to thalidomide? If clinical trials are promising and
the FDA is involved, what’s the problem?
What is Thalidomide?
Synthetic drug marketed as a sedative
Prescribed to pregnant women to help with morning sickness
Drug testing conducted on rats
Rats metabolized thalidomide
Late 1950’s children born with Pharcomelia
Later tests on monkeys produced same birth defects as seen in humans
References (excludes article screenshots)
Berry, L. (n.d.). Sierra Wild Flowers. Retrieved Oct 23, 2009, from Sierrawildflowers.org: http://www.sierrawildflowers.org/veratrum_californicum.htm
Binns, W. L. (1968). Effects of Teratogenic Agents in Range Plants. Cancer Research , 28, 2323-2326.
Keeley. (2002). Biology News. Retrieved Oct 23, 2009, from Bio-Medicine: http://news.bio-medicine.org/biology-news-2/Plant-compound-kills-brain-tumor-cells-6856-1/
Lingham, A. (2000, June). The First Appearance of Thalidomide. Retrieved Oct 23, 2009, from Thalidomide Isomerism and Optical Isomerism: http://www.chm.bris.ac.uk/motm/thalidomide/first.html
Wong, J. F. (2009). Genetic Engineering & Biotechnology News. Retrieved Oct 23, 2009, from GEN: http://www.genengnews.com/articles/chitem.aspx?aid=2518&chid=4