Denbinobin-mediated anticancer effect in human K562 leukemia cells: role in tubulin polymerization and Bcr-Abl activity

Denbinobin (5-hydroxy-3.7-diniethoxy-1,4-phenanthraquinone) has been reported to exhibit anti-tumor and anti-inflammatory activity. Nevertheless, the anti-tumor mechanism of denbinobin remains unclear. In the present study, we evaluated the anticancer activity of denbinobin in human myelogenous K562 leukemia cells. In accordance with the 3-[4,5-dimethylthiazol-2-yl]-2,5-diplienyl tetrazolium bromide (MTT) assay, we demonstrated that denbinobin inhibited cell viability in a concentration-dependent manner with an IC50 value of 1.84 mu M. Cell cycle analysis illustrated that exposure of denbinobin caused a G2/M phase accumulation in a time-dependent manner. Tubulin polymerization in cells was apparently enhanced by denbinobin, implying that denbinobin might have a regulatory role in tubulin/microtubule. Furthermore, denbinobin significantly suppressed the expression of Bcr-Ab1 and phosphorylation of CrkL, a crucial tyrosine kinase and an adaptor protein in chronic myelold leukemia, respectively. Denbinobin also markedly enhanced CD11b expression after a long-term treatment, suggesting that denbinobin might play a role in facilitating differentiation in K562 cells. In summary, we have demonstrated that denbinobin displays anticancer effects in K562 cells through the increase of levels of tubulin polymerization and deregulation of Bcr-Ab1 signaling. Our data demonstrate that denbinobin could be a potential anticancer lead compound for further development.