Differential Effects of Antofine N-Oxide on Solid Tumor and Leukemia Cells
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.
Keywords: Apoptosis, cytostasis, leukemia, microarrays, phenanthroindolizidine alkaloid, solid tumor, TNFα.
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