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Published on: September 18, 2013
Differential effects of antofine N-oxide on solid tumor and leukemia cells
Tania Bour, Xianwen Yang, Weihong Li
1Laboratory of Cellular and Molecular Oncology, Public Research Center for Health (CRP-Sante), L-1526 Luxembourg. tania.bour@crp-sante.lu.
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.
Insights
Antofine N-oxide from Cynanchum vincetoxicum effectively targets cancer cells. It inhibits solid tumor growth via TNFα signaling but induces apoptosis in leukemia through a different pathway.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Background:
- The medicinal plant Cynanchum vincetoxicum contains compounds with potential therapeutic properties.
- Antofine N-oxide is a purified compound from this plant with known biological activities.
Purpose of the Study:
- To investigate the anti-cancer activities of antofine N-oxide.
- To elucidate the molecular mechanisms underlying its effects on different cancer cell types.
Main Methods:
- Cytotoxicity assays on various solid tumor and leukemia cell lines.
- Microarray analysis to identify differentially expressed genes.
- Real-time quantitative PCR to validate gene expression changes.
- Functional analysis of signaling pathways.
Main Results:
- Antofine N-oxide exhibited potent cytotoxicity against glioblastoma, breast, and lung carcinoma cell lines, and T-cell leukemia.
- Solid tumor cells showed inhibited proliferation, while leukemia cells underwent apoptosis.
- Microarray analysis revealed significant gene expression changes in solid tumors, particularly involving TNFα signaling.
- TNFR1 signaling activation and increased mRNA levels of TNFα, TNFAIP3, and BIRC3 were confirmed in solid tumor cells.
Conclusions:
- Antofine N-oxide inhibits solid tumor cell proliferation primarily through TNFα signaling pathway activation.
- Leukemia cell apoptosis is induced by antofine N-oxide via a distinct, currently unknown pathway.
- These findings highlight antofine N-oxide as a promising agent with differential anti-cancer mechanisms.
