Acta Pharmacologica Sinica 2008 March; 29 (3): 349-354; doi: 10.1111/j.1745-7254.2008.00762.x

Aim: To explore the anticancer effects and the molecular mechanisms of gambogic acid (GA) on Jurkat cells.

Methods: Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assay. Annexin V-fluorescein-isothiocyanate/propidium iodide, DNA defragmentation, and comet assay were used to detect apoptosis. Western blotting was used to study the expression of death inducer-obliterator-1 (DIO-1), Bcl-2, NF-κB, and pro-caspase 3, as well as 2 activated subunits: p17 and p20. The subcellular localization of DIO-1 was examined by immunofluorescence and Hoechst33258 staining.

Results: GA inhibited the proliferation of Jurkat cells with 50% inhibitory concentration values of 1.51±0.09 (24 h), 0.98±0.13 (48 h), and 0.67±0.12 μmol/L (72 h). GA was able to induce apoptosis of Jurkat cells. Treated by GA, the expression of DIO-1 was upregulated, and that of Bcl-2 and NF-κB was downregulated, leading to the activation of pro-caspase 3. GA induced the translocation of DIO-1 to the nucleus.

Conclusion: GA suppressed the proliferation of Jurkat cells by apoptosis induction. DIO-1 triggered early-stage cell death in GA-treated Jurkat cells.

Keywords: gambogic acid; apoptosis; death inducer-obliterator 1; NF-κB