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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 suppressed the growth of human colon tumors in vivo. Nude mice bearing LoVo human colon xenografts were treated with physiological saline or curcumol at three doses (20, 40, 80 mg/kg of body weight) for 21 days. (a) Representative tumor pictures; (b) Tumor volume was recorded every three days; (c) Tumor weight was evaluated on the twenty-first day; (d) Body weight was recorded every three days; (e) Immunohistochemical staining of tumor specimens; and (f) The level of p38, phospho-p38 and CREB was analyzed by Western blot. Data are represented as mean ± SD; n = 6 mice per group. *p < 0.05 **p < 0.01 when compared with the untreated control group.
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ijms-16-19851-f006: Curcumol suppressed the growth of human colon tumors in vivo. Nude mice bearing LoVo human colon xenografts were treated with physiological saline or curcumol at three doses (20, 40, 80 mg/kg of body weight) for 21 days. (a) Representative tumor pictures; (b) Tumor volume was recorded every three days; (c) Tumor weight was evaluated on the twenty-first day; (d) Body weight was recorded every three days; (e) Immunohistochemical staining of tumor specimens; and (f) The level of p38, phospho-p38 and CREB was analyzed by Western blot. Data are represented as mean ± SD; n = 6 mice per group. *p < 0.05 **p < 0.01 when compared with the untreated control group.

Mentions: After assessing the anti-tumor activity of curcumol in colorectal cancer in vitro, further study was carried out to investigate the anti-tumor effects of curcumol in vivo. LoVo cells were xenografted subcutaneously into the right flanks of BALB/c nude mice to establish xenografts. Tumor-bearing mice were treated with vehicle or curcumol at a dosage of 20, 40 or 80 mg/kg/day for the LoVo model. Curcumol substantially suppressed tumor growth in a dose-dependent manner (Figure 6a); significant reductions in tumor volume (Figure 6b) and tumor weight (Figure 6c) were observed in the curcumol-treated groups, and, especially, tumor progression inhibition was nearly 70% in 80 mg/kg group. Furthermore, curcumol-treated groups were well tolerated and did not show significant loss in body weight (Figure 6d).


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 suppressed the growth of human colon tumors in vivo. Nude mice bearing LoVo human colon xenografts were treated with physiological saline or curcumol at three doses (20, 40, 80 mg/kg of body weight) for 21 days. (a) Representative tumor pictures; (b) Tumor volume was recorded every three days; (c) Tumor weight was evaluated on the twenty-first day; (d) Body weight was recorded every three days; (e) Immunohistochemical staining of tumor specimens; and (f) The level of p38, phospho-p38 and CREB was analyzed by Western blot. Data are represented as mean ± SD; n = 6 mice per group. *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-f006: Curcumol suppressed the growth of human colon tumors in vivo. Nude mice bearing LoVo human colon xenografts were treated with physiological saline or curcumol at three doses (20, 40, 80 mg/kg of body weight) for 21 days. (a) Representative tumor pictures; (b) Tumor volume was recorded every three days; (c) Tumor weight was evaluated on the twenty-first day; (d) Body weight was recorded every three days; (e) Immunohistochemical staining of tumor specimens; and (f) The level of p38, phospho-p38 and CREB was analyzed by Western blot. Data are represented as mean ± SD; n = 6 mice per group. *p < 0.05 **p < 0.01 when compared with the untreated control group.
Mentions: After assessing the anti-tumor activity of curcumol in colorectal cancer in vitro, further study was carried out to investigate the anti-tumor effects of curcumol in vivo. LoVo cells were xenografted subcutaneously into the right flanks of BALB/c nude mice to establish xenografts. Tumor-bearing mice were treated with vehicle or curcumol at a dosage of 20, 40 or 80 mg/kg/day for the LoVo model. Curcumol substantially suppressed tumor growth in a dose-dependent manner (Figure 6a); significant reductions in tumor volume (Figure 6b) and tumor weight (Figure 6c) were observed in the curcumol-treated groups, and, especially, tumor progression inhibition was nearly 70% in 80 mg/kg group. Furthermore, curcumol-treated groups were well tolerated and did not show significant loss in body weight (Figure 6d).

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