Curcumin Induces Growth Arrest And Apoptosis In Colon Cancer Cells
NewsRx.com
January 30, 2003
According to a study from the United States, "The development of nontoxic
natural agents with chemopreventive activity against colon cancer is the focus
of investigation in many laboratories. Curcumin (feruylmethane), a natural plant
product, possesses such chemopreventive activity, but the mechanisms by which it
prevents cancer growth are not well understood.
"In the present study, we examined the mechanisms by which curcumin treatment
affects the growth of colon cancer cells in vitro. Results showed that curcumin
treatment causes p53- and p21-independent G(2)/M phase arrest and apoptosis in
HCT-116(p53(+/+)), HCT-116(p53(-/-)) and HCT-116(p21(-/-)) cell lines. We
further investigated the association of the beta-catenin-mediated c-Myc
expression and the cell-cell adhesion pathways in curcumin-induced G(2)/M arrest
and apoptosis in HCT-116 cells.
"The results described a caspase-3-mediated cleavage of beta-catenin, decreased
transactivation of beta-catenin/Tcf-Lef, decreased promoter DNA binding activity
of the beta-catenin/Tcf-Lef complex, and decreased levels of c-Myc protein.
These activities were linked with decreased Cdc2/cyclin B1 kinase activity, a
function of the G2/M phase arrest. The decreased transactivation of beta-catenin
in curcumin-treated HCT-116 cells was unpreventable by caspase-3 inhibitor
Z-DEVD-fmk, even though the curcumin-induced cleavage of beta-catenin was
blocked in Z-DEVD-fmk pretreated cells," stated A.S. Jaiswal and colleagues,
University of Florida College of Medicine.
"The curcumin treatment also induced caspase-3-mediated degradation of cell-cell
adhesion proteins beta-catenin, E-cadherin and APC, which were linked with
apoptosis, and this degradation was prevented with the caspase-3 inhibitor. Our
results suggest that curcumin treatment impairs both Wnt signaling and cell-cell
adhesion pathways, resulting in G(2)/M phase arrest and apoptosis in HCT-116
cells," Jaiswal and colleagues concluded.
Jaiswal and colleagues published the results of their study in Oncogene
(beta-Catenin-mediated transactivation and cell - cell adhesion pathways are
important in curcumin (Diferuylmethane)-induced growth arrest and apoptosis in
colon cancer cells. Oncogene, 2002;21(55):8414-8427).
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