Denbinobin (5-hydroxy-3,7-dimethoxy-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-
diphenyl tetrazolium
bromide (MTT) assay, we demonstrated that
denbinobin inhibited cell viability in a concentration-dependent manner with an IC50 value of 1.84 microM. 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-Abl and phosphorylation of CrkL, a crucial
tyrosine kinase and an adaptor
protein in
chronic myeloid 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-Abl signaling. Our data demonstrate that
denbinobin could be a potential anticancer lead compound for further development.