Abstract
A human neuroblastoma cell line, IMR-32, was used as an in vitro model system to study the effects of arsenic trioxide (As(2)O(3)) on aggressive human neuroblastoma. From 0.5 micro M, As(2)O(3) exhibited a dose-dependent inhibition of IMR-32 proliferation. At concentrations of 1.5 micro M or higher, As(2)O(3) up-regulated caspase 3, leading to cellular apoptosis. However, neurofilament-200 kDa and tyrosine hydroxylase were not up-regulated, implying minimal neuronal differentiation. Concomitantly, TrkA was down-regulated and TrkB up-regulated. Pre-treatment with the protein kinase C (PKC) inhibitor Ro-31-8220 partially blocked As(2)O(3)-mediated apoptosis, meaning that As(2)O(3) might signal through PKC activation. The results suggest that As(2)O(3) might be potentially useful in neuroblastoma.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Apoptosis / drug effects*
-
Arsenic Trioxide
-
Arsenicals / pharmacology*
-
Blotting, Western
-
Cell Differentiation / drug effects*
-
Cell Line, Tumor
-
Cell Proliferation / drug effects*
-
Dose-Response Relationship, Drug
-
Down-Regulation / drug effects
-
Enzyme Activation / drug effects
-
Growth Inhibitors / pharmacology
-
Humans
-
Indoles / pharmacology
-
Neuroblastoma / enzymology
-
Neuroblastoma / metabolism
-
Neuroblastoma / pathology
-
Neurofilament Proteins / metabolism
-
Neurons / drug effects
-
Neurons / metabolism
-
Neurons / pathology
-
Oxides / pharmacology*
-
Protein Kinase C / antagonists & inhibitors
-
Protein Kinase C / metabolism
-
Receptor, trkA / metabolism
-
Receptor, trkB / metabolism
-
Tyrosine 3-Monooxygenase / metabolism
-
Up-Regulation / drug effects
Substances
-
Arsenicals
-
Growth Inhibitors
-
Indoles
-
Neurofilament Proteins
-
Oxides
-
neurofilament protein H
-
Tyrosine 3-Monooxygenase
-
Receptor, trkA
-
Receptor, trkB
-
Protein Kinase C
-
Arsenic Trioxide
-
Ro 31-8220