Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210~(bcr/abl)-initiated Ras signal transduction pathway

摘要

AIM: To investigate the effects of curcumin (Cur) on proliferation of K562 cells and the relationship between these effects and Ras signal transduction pathway activated by p210~(bcr/abl). METHODS: K562 cell line was used as a p210~(bcr/abl)-positive cell system and HL-60 cell line as a p210~(bcr/abl)-negative control; etoposide (VP-16), which has no influence on p210~(bcr/abl) and has resistance to K562 cells, was used as an anticancer drug control to compare withcurcumin. MTT was used to determine the proliferative effects of drugs on K562 and HL-60 cells. Western blot and flow cytometry were used to examine the abundance of signal protein molecules expressed in tumor cells. RESULTS: An exposure of K562 cells or HL-60 cells to Cur produced both concentration- and time-dependent increase in the anti-proliferative rate. Moreover, both cell lines had the same sensitivity to Cur (P>0.05). In contrast, HL-60 cells had more sensitivity to VP-16 than K562 cells in anti-proliferative effect (P<0.01). The abundance of p210~(bcr/abl) as well as MEK-1 and c-JUN proteins were strongly down-regulated in curcumin-treated p210~(bcr/abl)-positive K562 cells while c-JUN and MEK-1 proteins were only slightly down-regulated in p210~(bcr/abl)-negative HL-60 cells. CONCLUSION: Curcumin inhibited the proliferation of K562 cells and the inhibitory effect was correlated with down-regulation of the abundance of p210~(bcr/abl), which may ultimately lead to retard the Ras signal transduction pathway. Curcumin might be worthy of being evaluated as a potential chemotherapeutic agent to CML.