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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 down-regulated the expression of IGF-1R in human colorectal cancer cells. The mRNA expression of IGF-1R was detected by real-time PCR (a) and RT-PCR (b); (c) The expression of IGF-1R was analyzed by Western blot. Cells were treated with curcumol for 48 h, and total proteins were extracted. Equal protein loading was evaluated by β-actin. Data are represented as means ± S.D. from at least of three independent experiments. *p < 0.05, **p < 0.01 when compared with the untreated control group.
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ijms-16-19851-f004: Curcumol down-regulated the expression of IGF-1R in human colorectal cancer cells. The mRNA expression of IGF-1R was detected by real-time PCR (a) and RT-PCR (b); (c) The expression of IGF-1R was analyzed by Western blot. Cells were treated with curcumol for 48 h, and total proteins were extracted. Equal protein loading was evaluated by β-actin. Data are represented as means ± S.D. from at least of three independent experiments. *p < 0.05, **p < 0.01 when compared with the untreated control group.

Mentions: A functional IGF-1R caused anchorage-independent growth in various cancers and activated proliferation and survival signaling pathway [12,23,24]. Numerous studies indicated that IGF-1R may be a promising target for tumor therapy. It has been reported that IGF-1R was overexpressed in more than 90% colorectal carcinomas, which contributed to the malignant characteristics of aggressive growth and poor prognosis [14,25]. To investigate IGF-1R activity in colorectal carcinomas cells following curcumol treatment, the transcription level of IGF-1R was analyzed by the RT-PCR and quantitative real time PCR. We found that increasing concentrations of curcumol decreased IGF-1R mRNA level (Figure 4a,b). Furthermore, we examined the IGF-1R changes at protein level by Western blotting (Figure 4c). As shown in Figure 4c, after treatment with curcumol for 48 h, the protein levels of IGF-1R decreased dose-dependently.


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 down-regulated the expression of IGF-1R in human colorectal cancer cells. The mRNA expression of IGF-1R was detected by real-time PCR (a) and RT-PCR (b); (c) The expression of IGF-1R was analyzed by Western blot. Cells were treated with curcumol for 48 h, and total proteins were extracted. Equal protein loading was evaluated by β-actin. Data are represented as means ± S.D. from at least of three independent experiments. *p < 0.05, **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-f004: Curcumol down-regulated the expression of IGF-1R in human colorectal cancer cells. The mRNA expression of IGF-1R was detected by real-time PCR (a) and RT-PCR (b); (c) The expression of IGF-1R was analyzed by Western blot. Cells were treated with curcumol for 48 h, and total proteins were extracted. Equal protein loading was evaluated by β-actin. Data are represented as means ± S.D. from at least of three independent experiments. *p < 0.05, **p < 0.01 when compared with the untreated control group.
Mentions: A functional IGF-1R caused anchorage-independent growth in various cancers and activated proliferation and survival signaling pathway [12,23,24]. Numerous studies indicated that IGF-1R may be a promising target for tumor therapy. It has been reported that IGF-1R was overexpressed in more than 90% colorectal carcinomas, which contributed to the malignant characteristics of aggressive growth and poor prognosis [14,25]. To investigate IGF-1R activity in colorectal carcinomas cells following curcumol treatment, the transcription level of IGF-1R was analyzed by the RT-PCR and quantitative real time PCR. We found that increasing concentrations of curcumol decreased IGF-1R mRNA level (Figure 4a,b). Furthermore, we examined the IGF-1R changes at protein level by Western blotting (Figure 4c). As shown in Figure 4c, after treatment with curcumol for 48 h, the protein levels of IGF-1R decreased dose-dependently.

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