N-Myc knockdown and apigenin treatment controlled growth of malignant neuroblastoma cells having N-Myc amplification.
Malignant neuroblastomas mostly occur in children and are frequently associated with N-Myc amplification. Oncogene amplification, which is selective increase in copy number of the oncogene, provides survival advantages in solid tumors including malignant neuroblastoma. We have decreased expression of N-Myc oncogene using short hairpin RNA (shRNA) plasmid to increase anti-tumor efficacy of the isoflavonoid apigenin (APG) in human malignant neuroblastoma SK-N-DZ and SK-N-BE2 cell lines that harbor N-Myc amplification. N-Myc knockdown induced morphological and biochemical features of neuronal differentiation. Combination of N-Myc knockdown and APG most effectively induced morphological and biochemical features of apoptotic death. This combination therapy also prevented cell migration and decreased N-Myc driven survival, angiogenic, and invasive factors. Collectively, N-Myc knockdown and APG treatment is a promising strategy for controlling the growth of human malignant neuroblastoma cell lines that harbor N-Myc amplification.
University of South Carolina School of Medicine, Department of Pathology, Microbiology, and Immunology, Columbia, SC 29209, USA.
Md Motarab
MM
Hossain
Naren L
NL
Banik
Swapan K
SK
Ray
D000970:Antineoplastic Agents / Q000494:pharmacology*; D047310:Apigenin / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3 / Q000235:genetics / Q000378:metabolism; D053181:Caspase 8 / Q000235:genetics / Q000378:metabolism; D002454:Cell Differentiation / Q000187:drug effects; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D055785:Gene Knockdown Techniques; D006801:Humans; D009447:Neuroblastoma / Q000235:genetics* / Q000473:pathology; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D034741:RNA, Small Interfering / Q000235:genetics / Q000378:metabolism; D014162:Transfection
D000970:Antineoplastic Agents; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D047310:Apigenin; C505407:CASP3 protein, human; C505530:CASP8 protein, human; D053148:Caspase 3; D053181:Caspase 8
4′,6-diamidino-2-phenylindole; APG; Apigenin; Apoptosis; BSA; CTL; DAPI; Differentiation; FITC; GAPDH; HRP; ICAD; ID2; MMP-2; N-Myc shRNA; NF-κB; NFP; NSE; Neuroblastoma; PBS; PCNA; PI; PVDF; RT-PCR; SBDP; SDS-PAGE; VEGF; apigenin; b-FGF; basic fibroblast growth factor; bovine serum albumin; control; fluorescein isothocyanate; glyceraldehyde 3-phosphate dehydrogenase; hTERT; horseradish peroxidase; human telomerase reverse transcriptase; inhibitor of caspase-activated DNase; inhibitor of differentiation 2; matrix metalloproteinase-2; neurofilament protein; neuron specific enolase; nuclear factor-kappa B; phosphate-buffered saline; polyvinylidene fluoride; proliferating cell nuclear antigen; propidium iodide; reverse transcription-polymerase chain reaction; shRNA; short hairpin RNA; sodium dodecyl sulfate-polyacrylamide gel electrophoresis; spectrin breakdown product; vascular endothelial growth factor