Arsenic trioxide

Zn finger domains from the human GLI oncogene bind DNA

GLI protein bound to DNA

I previously mentioned that arsenic is a carcinogen, but arsenic trioxide is an FDA-approved drug used for the treatment of acute promyelocytic leukemia. How does arsenic trioxide function to control the growth of some cancerous cells?

A signal transduction pathway that has been implicated in the growth of some tumors is the Hedgehog pathway. The Hedgehog pathway is famous for its role in embryonic development. For example, livestock that consume plants such as Veratrum californicum are likely to give birth to offspring that show cyclopia.

Structure of arsenic trioxide

Arsenic trioxide

The GLI transcription factors are regulated by the Hedgehog pathway. This past summer it was reported that “Arsenic antagonizes the Hedgehog pathway by reducing stability of the GLI2 transcriptional effector“. It has now also been reported that “Arsenic trioxide inhibits human cancer cell growth and tumor development in mice by blocking Hedgehog/GLI pathway“. In this newer article, it is suggested by Elspeth Beauchamp et al that arsenic trioxide binds to GLI1 protein and might alter protein-protein interactions of transcriptional coactivators that bind to GLI1.
RelatedCase of true cyclopia

Sweet fruit from a poisonous kiss

What happens to arsenic trioxide in the body.

Image credits. The image is a cartoon representation of a protein interacting with DNA:  FIVE-FINGER GLI/DNA COMPLEX by N. P. Pavletich and C. O. Pabo

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About johnwschmidt

Exploring medical physiology.
This entry was posted in acute promyelocytic leukemia, Arsenic, cancer, cyclopia, Hedgehog pathway and tagged , . Bookmark the permalink.

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