Inhibitory effect of curcumin on proliferation of K562 cells involves down-regulation of p210(bcr/abl) initiated Ras signal transduction pathway.
OBJECTIVE
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 p210bcr/abl.


METHODS
K562 cell line was used as a p210bcr/abl-positive cell system and HL-60 cell line as a p210bcr/abl-negative control; etoposide (VP-16), which has no influence on p210bcr/abl and has resistance to K562 cells[1], was used as an anticancer drug control to compare with curcumin. 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 p210bcr/abl as well as MEK-1 and c-JUN proteins were strongly down-regulated in curcumin-treated p210bcr/abl-positive K562 cells while c-JUN and MEK-1 proteins were only slightly down-regulated in p210bcr/abl-negative HL-60 cells.


CONCLUSIONS
Curcumin inhibited the proliferation of K562 cells and the inhibitory effect was correlated with down-regulation of the abundance of p210bcr/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.
Wu
Li-Xian
LX
Department of Pharmacology, Institute of Clinical Pharmacology, Fujian Medical University, Fuzhou 350004, China. jhx58@hotmail.com
Xu
Jian-Hua
JH
Wu
Guo-Hua
GH
Chen
Yuan-Zhong
YZ
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D003474:Curcumin / Q000494:pharmacology*; D015536:Down-Regulation; D016044:Fusion Proteins, bcr-abl / Q000378:metabolism*; D011905:Genes, ras; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D020014:K562 Cells / Q000187:drug effects; D015398:Signal Transduction / Q000187:drug effects*
D000972:Antineoplastic Agents, Phytogenic; D016044:Fusion Proteins, bcr-abl; D003474:Curcumin