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Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.

Wang J, Huang F, Bai Z, Chi B, Wu J, Chen X - Int J Mol Sci (2015)

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Guilin Medical University, Guilin 541004, China. wujiacaiwjc@hotmail.com.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus

Curcumol inhibited human colorectal cancer cell viability. (a) Cell colony formation was evaluated by clonogenic assay; and (b) Statistical results of colony-forming assays presented as surviving colonies (percentage of untreated control). Data are expressed as mean ± SD from at least three independent experiments, **p < 0.01 when compared with the untreated control group.
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ijms-16-19851-f002: Curcumol inhibited human colorectal cancer cell viability. (a) Cell colony formation was evaluated by clonogenic assay; and (b) Statistical results of colony-forming assays presented as surviving colonies (percentage of untreated control). Data are expressed as mean ± SD from at least three independent experiments, **p < 0.01 when compared with the untreated control group.

Mentions: To further evaluate the inhibition effect of curcumol on cell viability, after curcumol treatment colony-formation assay was performed. As shown in Figure 2a,b, curcumol showed a significant inhibition on colony formation in a dose-dependent manner when compared with control group, and at a concentration of 0.4 μΜ/mL curcumol, nearly no colonies were detected. The results from clonogenic assay demonstrated that curcumol could significantly inhibit the colorectal cancer reproductive potentials compared with the control group, which were consistent with the result from MTT assay.


Curcumol Inhibits Growth and Induces Apoptosis of Colorectal Cancer LoVo Cell Line via IGF-1R and p38 MAPK Pathway.

Wang J, Huang F, Bai Z, Chi B, Wu J, Chen X - Int J Mol Sci (2015)

Curcumol inhibited human colorectal cancer cell viability. (a) Cell colony formation was evaluated by clonogenic assay; and (b) Statistical results of colony-forming assays presented as surviving colonies (percentage of untreated control). Data are expressed as mean ± SD from at least three independent experiments, **p < 0.01 when compared with the untreated control group.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4581329&req=5

ijms-16-19851-f002: Curcumol inhibited human colorectal cancer cell viability. (a) Cell colony formation was evaluated by clonogenic assay; and (b) Statistical results of colony-forming assays presented as surviving colonies (percentage of untreated control). Data are expressed as mean ± SD from at least three independent experiments, **p < 0.01 when compared with the untreated control group.
Mentions: To further evaluate the inhibition effect of curcumol on cell viability, after curcumol treatment colony-formation assay was performed. As shown in Figure 2a,b, curcumol showed a significant inhibition on colony formation in a dose-dependent manner when compared with control group, and at a concentration of 0.4 μΜ/mL curcumol, nearly no colonies were detected. The results from clonogenic assay demonstrated that curcumol could significantly inhibit the colorectal cancer reproductive potentials compared with the control group, which were consistent with the result from MTT assay.

Bottom Line: 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.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmacy, Guilin Medical University, Guilin 541004, China. wujiacaiwjc@hotmail.com.

ABSTRACT
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.

No MeSH data available.


Related in: MedlinePlus