A New Era for an Ancient Drug. Arsenic Trioxide and Hedgehog Signaling

Elspeth M. Beauchamp*, Aykut Üren

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

18 Scopus citations

Abstract

Arsenic has been used for ages as a therapeutic agent. Currently, it is an FDA approved drug to treat acute promyelocytic leukemia where it leads to degradation of the PML-RAR fusion protein. It has been shown to have various other targets in cells such as JNK, NFκB, thioredoxin reductase, and MAPK pathways. Most of its effects in cells have been through arsenic's ability to bind to thiol groups in cysteine residues. Recent evidence has shown that arsenic can inhibit the Hedgehog pathway by inhibiting GLI proteins. The proposed mechanism of action is through direct binding. Potential binding sites include the critical cysteine residues in GLI zinc finger domains. The role of the Hedgehog pathway has been implicated in many cancers such as basal cell carcinoma, medulloblastoma, Ewing sarcoma, and rhabdoid tumors. Current Hedgehog pathway inhibitors have been fraught with resistance issues and so arsenic trioxide may provide an alternative therapy when combined with these other inhibitors or after acquired resistance.

Original languageEnglish (US)
Pages (from-to)333-354
Number of pages22
JournalVitamins and Hormones
Volume88
DOIs
StatePublished - Mar 7 2012

Keywords

  • Arsenic
  • Cancer
  • Ewing sarcoma
  • GLI
  • Hedgehog
  • Leukemia
  • Medulloblastoma

ASJC Scopus subject areas

  • Endocrinology
  • Physiology

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