- 作者: Yu-Chun Huang; Jih-Hwa Guh ; Che-Ming Teng
- 作者服務機構: 1 Pharmacological Institute and;; 2 School of Pharmacy, College of Medicine, National Taiwan University, No. 1, Jen-Ai Road, Sect. 1, Taipei, Taiwan
- 中文摘要: --
- 英文摘要: Denbinobin (5-hydroxy-3,7-dimethoxy-l,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 μM. 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 CD1 1b 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.
- 中文關鍵字: --
- 英文關鍵字: apoptosis, Bcr-Abl, denbinobin, mitotic arrest, tubulin polymerization