Arsenic trioxide inhibits cell growth in SH-SY5Y and SK-N-AS neuroblastoma cell lines by a different mechanism.
Neuroblastoma, characterized by heterogeneous cell population, is a common solid tumor in childhood and some malignant neuroblastomas are refractory to conventional chemotherapy. Recently, treatment with arsenic trioxide (As2O3) was found effective in the treatment of acute promyelocytic leukemia as well as neuroblastoma cells by inducing apoptosis. To define the mechanism contributing to cell death in those heterogenous cell populations, the authors used two different types of neuroblastoma cells, SH-SY5Y and SK-N-AS, to compare the pathways that mediate death response to arsenic trioxide. With arsenic trioxide exposure, both cell lines were arrested at the S-G2/M phase with the increase of cyclin B expression and CDK1 activity. Although caspase 3 was activated in both cell lines, the NF-kappaB activity and the expression of cyclin D1, cyclin E, and p27 were different. Therefore, arsenic trioxide could be an effective cytotoxic drug for the treatment of heterogeneous cellular population of neuroblastoma.
Woo
So-Youn
SY
Department of Microbiology, Ewha Medical Research Institute, Ewha Woman's University, College of Medicine, Seoul, Korea.
Lee
Mi-Young
MY
Jung
Yun-Jae
YJ
Yoo
Eun-Sun
ES
Seoh
Ju-Young
JY
Shin
Hee-Young
HY
Ahn
Hyo-Seop
HS
Ryu
Kyung-Ha
KH
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology*; D016203:CDC2 Protein Kinase / Q000096:biosynthesis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000096:biosynthesis / Q000235:genetics; D018844:Cyclin-Dependent Kinases / Q000096:biosynthesis / Q000235:genetics; D016213:Cyclins / Q000096:biosynthesis / Q000235:genetics; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D016195:G2 Phase / Q000187:drug effects; D005786:Gene Expression Regulation / Q000187:drug effects*; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D008677:Metaphase / Q000187:drug effects; D016328:NF-kappa B / Q000378:metabolism*; D009363:Neoplasm Proteins / Q000096:biosynthesis / Q000235:genetics; D009447:Neuroblastoma / Q000473:pathology*; D018384:Oxidative Stress; D010087:Oxides / Q000494:pharmacology*; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D016196:S Phase / Q000187:drug effects
D000970:Antineoplastic Agents; D001152:Arsenicals; D016213:Cyclins; D016328:NF-kappa B; D009363:Neoplasm Proteins; D010087:Oxides; D019253:Proto-Oncogene Proteins c-bcl-2; D050760:Cyclin-Dependent Kinase Inhibitor p27; D011065:Poly(ADP-ribose) Polymerases; D016203:CDC2 Protein Kinase; D018844:Cyclin-Dependent Kinases; C505407:CASP3 protein, human; D053148:Caspase 3; D020169:Caspases; D000077237:Arsenic Trioxide