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Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell
Line via IGF-1R and p38 MAPK Pathway
#MMPMID26307972
Wang J
; Huang F
; Bai Z
; Chi B
; Wu J
; Chen X
Int J Mol Sci
2015[Aug]; 16
(8
): 19851-67
PMID26307972
show ga
Curcumol, isolated from the traditional medical plant Rhizoma Curcumae, is the
bioactive component of Zedoary oil, whose potential anti-tumor effect has
attracted considerable attention in recent years. Though many researchers have
reported curcumol and its bioactivity, the potential molecular mechanism for its
anti-cancer effect in colorectal cancer LoVo cells still remains unclear. In the
present study, we found that curcumol showed growth inhibition and induced
apoptosis of LoVo cells in a dose- and time-dependent manner. The occurrence of
its proliferation inhibition and apoptosis came with suppression of IGF-1R
expression, and then increased the phosphorylation of p38 mitogen activated
protein kinase (MAPK), which might result in a cascade response by inhibiting the
CREB survival pathway and finally triggered Bax/Bcl-2 and poly(ADP-ribose)
polymerase 1 (PARP-1) apoptosis signals. Moreover, curcumol inhibited colorectal
cancer in xenograft models of nude mice. Immunohistochemical and Western blot
analysis revealed that curcumol could decrease the expression of ki-67, Bcl-2 as
well as CREB1, and increase the expression of Bax and the phosphorylation of p38,
which were consistent with our in vitro study. Overall, our in vitro and in vivo
data confirmed the anti-cancer activity of curcumol, which was related to a
significant inhibition of IGF-1R and activation of p38 MAPKs, indicating that
curcumol may be a potential anti-tumor agent for colorectal carcinoma therapy.
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