Transcription profiling by array of several human solid tumor cell lines (glioblastoma, breast carcinoma and lung carcinoma) and T-cell leukemia cells treated with different dose of antofine N-oxide to study the drug's anti-cancer activities

We have studied the anti-cancer activities of antofine N-oxide isolated and purified from the medicinal plant Cynanchum vincetoxicum. The compound displays a strong cytotoxic effect on several solid tumor cell lines (glioblastoma, breast carcinoma and lung carcinoma) and on T-cell leukemia. It induces cytostasis in the solid tumor cell lines whereas it causes apoptotic cell death in the leukemia cell line. The cytotoxic effect is much weaker in non-cancer control cells. A microarray analysis of the gene expression after a short treatment showed a set of differentially expressed genes in the two types of cancer cells (apoptosis versus cytostasis). Interestingly, a number of genes of the TNF-alpha signaling pathway are up-regulated in the three solid tumor cell lines, including TNF-alpha which is among the most significantly up-regulated genes. The increased TNF-alpha, TNFAIP3 and BIRC3 mRNA levels were further confirmed after different treatment durations by real-time quantitative PCR (qPCR). Our results suggest that inhibition of cell proliferation in solid tumor cells essentially occurs through TNF-alpha signaling whereas no conclusion could be drawn concerning the pathways leading to apoptotic cell death in leukemia cells due to the reduced number of differentially expressed genes.