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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 induced apoptosis in human colorectal cancer cells. (a) Cells were treated with curcumol for 48 h and analyzed by flow cytometry after AnnexinV-FITC/PI staining; (b) Statistical results of apoptosis assays by FCM presented as surviving cells (percentage of untreated control); (c) Cells were treated with curcumol for 48 h and analyzed after Hoechst 33258 staining; and (d,e) Bax, Bcl-2 and PARP involved in apoptosis were analyzed by Western blotting. 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 ± SD 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-f003: Curcumol induced apoptosis in human colorectal cancer cells. (a) Cells were treated with curcumol for 48 h and analyzed by flow cytometry after AnnexinV-FITC/PI staining; (b) Statistical results of apoptosis assays by FCM presented as surviving cells (percentage of untreated control); (c) Cells were treated with curcumol for 48 h and analyzed after Hoechst 33258 staining; and (d,e) Bax, Bcl-2 and PARP involved in apoptosis were analyzed by Western blotting. 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 ± SD from at least of three independent experiments. *p < 0.05, **p < 0.01 when compared with the untreated control group.

Mentions: Furthermore, in order to determine whether the inhibition effect of curcumol on colorectal cancer cells is associated with triggering the programmed cell death pathways, we then analyzed the apoptosis-induction effect of curcumol in LoVo cells. As shown in Figure 3c, the LoVo cells exhibited apoptotic features after treatment with curcumol by Hoechst 33,258 staining. Cells with bright-blue fluorescent condensed nuclei, reduction of cell volume and nuclear fragmentation were obviously observed at 0.4 μΜ/mL curcumol, however, almost none were found in the control group. To confirm the quantity of cell death, Annexin V-FITC and PI fluorescence staining assay were performed by flow cytometry. As shown in Figure 3a,b, curcumol induced LoVo cells apoptosis in a dose-dependent manner at 48 h. Meanwhile, Western blotting results (Figure 3d,e) showed that curcumol decreased the expression of Bcl-2 in an obvious concentration-dependent manner, while significantly increased the expression of bax and cleaved PARP-1.


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 induced apoptosis in human colorectal cancer cells. (a) Cells were treated with curcumol for 48 h and analyzed by flow cytometry after AnnexinV-FITC/PI staining; (b) Statistical results of apoptosis assays by FCM presented as surviving cells (percentage of untreated control); (c) Cells were treated with curcumol for 48 h and analyzed after Hoechst 33258 staining; and (d,e) Bax, Bcl-2 and PARP involved in apoptosis were analyzed by Western blotting. 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 ± SD 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-f003: Curcumol induced apoptosis in human colorectal cancer cells. (a) Cells were treated with curcumol for 48 h and analyzed by flow cytometry after AnnexinV-FITC/PI staining; (b) Statistical results of apoptosis assays by FCM presented as surviving cells (percentage of untreated control); (c) Cells were treated with curcumol for 48 h and analyzed after Hoechst 33258 staining; and (d,e) Bax, Bcl-2 and PARP involved in apoptosis were analyzed by Western blotting. 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 ± SD from at least of three independent experiments. *p < 0.05, **p < 0.01 when compared with the untreated control group.
Mentions: Furthermore, in order to determine whether the inhibition effect of curcumol on colorectal cancer cells is associated with triggering the programmed cell death pathways, we then analyzed the apoptosis-induction effect of curcumol in LoVo cells. As shown in Figure 3c, the LoVo cells exhibited apoptotic features after treatment with curcumol by Hoechst 33,258 staining. Cells with bright-blue fluorescent condensed nuclei, reduction of cell volume and nuclear fragmentation were obviously observed at 0.4 μΜ/mL curcumol, however, almost none were found in the control group. To confirm the quantity of cell death, Annexin V-FITC and PI fluorescence staining assay were performed by flow cytometry. As shown in Figure 3a,b, curcumol induced LoVo cells apoptosis in a dose-dependent manner at 48 h. Meanwhile, Western blotting results (Figure 3d,e) showed that curcumol decreased the expression of Bcl-2 in an obvious concentration-dependent manner, while significantly increased the expression of bax and cleaved PARP-1.

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