Objective: To explore the inhibitory effect of alantolactone on the proliferation of adriamycin-resistant human chronic myelogenous leukemia cell line K562/ADR cells and its mechanism.
Methods: K562/ADR cells were treated with various concentrations of alantolactone (0, 1, 2, 4, 6, 8, and 10 μmol/L) for different time points. Cell viability was analyzed with MTT assay. The effect of alantolactone on the apoptosis of K562/ADR cells was measured by flow cytometry. The expression of apoptosis-related proteins after treatment with alantolactone was analyzed using Western blot.
Results: Alantolactone could effectively inhibit the proliferation of K562/ADR cells in dose- and time- dependent manner, the IC50 value of alantolactone treatment of K562/ADR cells for 24 h was 4.7 μmol/L (P<0.05). Flow cytometric analysis displayed that the apoptotic rates were 1.35%, 16.91%, 29.61% and 46.26%, respectively, after treatment with alantolactone at 0, 2.5, 5 and 7.5 μmol/L. Meanwhile, the expression of Bcl-2 and BCR-ABL proteins were significantly decreased and that of Bax, cytochrome C, cleaved-caspase-9, cleaved-caspase-3 and cleaved-PARP increased by alantolactone treatment.
Conclusion: Alantolactone had obvious inhibitory effect on the proliferation of K562/ADR cells through the caspase dependent mitochondrial(or intrinsic)apoptotic pathway.