Regulation of gambogic acid on hERG potassium channel protein of K562 leukemia cells

Abstract

Objective: To explore the effects of gambogic acid (GA) on proliferation, apoptosis, and cell cycle distribution of leukemia cells K562, as well as to observe its regulation on the expression of human ether-à-go-go related genes (hKRG) protein. Methods: K562 Cells were treated with various concentration of GA (0. 125 - 8. 0 μmol/L) for 0 - 72 h. MTT Assay was used to evalute the inhibition of GA on the growth of K562 cells. Cell apoptosis was detected through both Annexin-V/P1 double-labeled cytometry and transmission electron microscopy (TEC). Cell cycle regulation was studied by a propidium iodide method. Western blotting and RT-PCR technologies were applied to assess the regulation on the expression level of hKRG in K562 cells. Results: GA presented striking growth inhibition on the proliferation of K562 cells in vitro in a time- and dose-dependent manner. The IC50 value of GA for 24 h was (2. 637 ± 0. 208) μmol/L. Moreover, GA induced K562 cells apoptosis in a dose-dependent manner and companied with the obvious morphological changes of apoptosis. Meanwhile, the apoptosis induction potency of CA on K562 cells might correlate well with its effect on the G 0/G1 cell cycle arrest. Overexpression of hKRG potassium channel protein was found in K562 cells, while GA could downregulate it at both protein and mRNA level in a dose-dependent manner (P < 0. 01). Conclusion: CA could exhibit its anti-leukemia effects partially through the downregulation of the protein expression level of hERG potassium channel in K562 cells, which suggests that hKRG potassium channel might be a new target for future therapy of leukemia.