Effects of arsenic trioxide on the cellular proliferation, apoptosis and differentiation of human neuroblastoma cells.
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.
Department of Medicine, The University of Hong Kong, Queen Mary Hospital, Hong Kong, China.
William M W
WM
Cheung
Patrick W K
PW
Chu
Yok L
YL
Kwong
D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D015153:Blotting, Western; D002454:Cell Differentiation / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D006131:Growth Inhibitors / Q000494:pharmacology; D006801:Humans; D007211:Indoles / Q000494:pharmacology; D009447:Neuroblastoma / Q000201:enzymology / Q000378:metabolism / Q000473:pathology; D016900:Neurofilament Proteins / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D010087:Oxides / Q000494:pharmacology*; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism; D020917:Receptor, trkA / Q000378:metabolism; D020813:Receptor, trkB / Q000378:metabolism; D014446:Tyrosine 3-Monooxygenase / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
D001152:Arsenicals; D006131:Growth Inhibitors; D007211:Indoles; D016900:Neurofilament Proteins; D010087:Oxides; C051774:neurofilament protein H; D014446:Tyrosine 3-Monooxygenase; D020917:Receptor, trkA; D020813:Receptor, trkB; D011493:Protein Kinase C; D000077237:Arsenic Trioxide; C064758:Ro 31-8220