title: Differential effects of antofine N-oxide on solid tumor and leukemia cells.
abstract: We have studied the anti-cancer activities of antofine N-oxide isolated and purified from the medicinal plant Cynanchum vincetoxicum. Antofine N-oxide displayed a strong inhibitory effect on several solid tumor cell lines (glioblastoma, breast carcinoma and lung carcinoma) and on a T-cell leukemia cell line. Remarkably, its cytotoxic effect was considerably weaker in non-cancer cells. Antofine N-oxide was found to inhibit proliferation of the solid tumor cells whereas it caused apoptotic cell death in the leukemia cells. A microarray analysis after a short treatment revealed that the number of differentially expressed genes was considerably higher in solid tumor than in leukemia cells. Up-regulated genes in the three solid tumor cell lines include genes related to TNFα signaling, of which TNFα was among the most significantly induced. A functional analysis revealed that TNFR1 signaling was most likely activated in the solid tumor cells. The increased mRNA levels of several genes of this pathway (namely TNFα, TNFAIP3 and BIRC3) were confirmed by real-time quantitative PCR after different treatment durations. Finally a slight inhibition of NFκB-mediated transcription was observed in the same cells. Together our results suggest that inhibition of cell proliferation in solid tumor cells essentially occurs through TNFα signaling whereas this pathway is not activated in leukemia cells. Apoptotic cell death in the latter is induced by a distinct yet unknown pathway.
authors: Tania
authors: T
authors: Bour
authors: Xianwen
authors: X
authors: Yang
authors: Weihong
authors: W
authors: Li
authors: Francois
authors: F
authors: Bernardin
authors: Tony
authors: T
authors: Kaoma
authors: Arnaud
authors: A
authors: Muller
authors: Laurent
authors: L
authors: Vallar
authors: Laboratory of Cellular and Molecular Oncology, Public Research Center for Health (CRP-Sante), L-1526 Luxembourg. tania.bour@crp-sante.lu.
authors: André
authors: A
authors: Steinmetz
mesh_terms: D000470:Alkaloids / Q000302:isolation & purification / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D031105:Cynanchum / Q000737:chemistry*; D020869:Gene Expression Profiling; D005909:Glioblastoma; D006801:Humans; D007212:Indolizines / Q000302:isolation & purification / Q000494:pharmacology*; D015458:Leukemia, T-Cell; D008175:Lung Neoplasms; D016328:NF-kappa B / Q000378:metabolism; D010616:Phenanthrenes / Q000302:isolation & purification / Q000494:pharmacology*; D012333:RNA, Messenger / Q000378:metabolism; D047888:Receptors, Tumor Necrosis Factor, Type I / Q000378:metabolism; D015398:Signal Transduction; D014158:Transcription, Genetic; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism
chemical_list: C420907:10-antofine N-oxide; D000470:Alkaloids; D000972:Antineoplastic Agents, Phytogenic; D007212:Indolizines; D016328:NF-kappa B; D010616:Phenanthrenes; D012333:RNA, Messenger; D047888:Receptors, Tumor Necrosis Factor, Type I; D014409:Tumor Necrosis Factor-alpha