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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 proliferation of human colorectal cancer cell. (a) Dose- and time-dependent inhibition effect of cucumol on LoVo cells was evaluated by MTT assay; and (b) Dose- and time-dependent inhibition effect of cucumol on SW 480 cells was evaluated by MTT assay. Data represent mean ± SD from at least three independent experiments. *p < 0.05 when compared with the untreated control group.
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ijms-16-19851-f001: Curcumol inhibited proliferation of human colorectal cancer cell. (a) Dose- and time-dependent inhibition effect of cucumol on LoVo cells was evaluated by MTT assay; and (b) Dose- and time-dependent inhibition effect of cucumol on SW 480 cells was evaluated by MTT assay. Data represent mean ± SD from at least three independent experiments. *p < 0.05 when compared with the untreated control group.

Mentions: In recent years, more and more cancer therapeutics on the market or in preclinical trails turn to natural products with low toxicity and drug resistance. Chinese people have used the medicinal plant Rhizoma Curcumae for thousands of years. Curcumol (Figure 1a) with the structure of a guaiane-type sesquiterpenoid hemiketal, has been reported to possess antitumor, antiproliferation, anti-inflammatory, anti-hepatic fibrosis, antioxidant, and antimicrobial activities with low cytotoxicity [6,7]. Recently, it has been reported that curcumol exhibited growth inhibitory and induced apoptosis activity in several human cancer cell lines in vitro, including cervical carcinoma, breast carcinoma, lung carcinoma, gastric carcinoma and hepatocarcinoma [8,9]. Chen found that 300 μM of curcumol could induce HSC-T6 apoptosis, while showing little toxicity to the normal liver cell line BRL-3A [10]. Tang found that curcumol (60 mg/kg) did not cause notable toxicity to the nude mouse [11]. Despite the increasing interest in the anti-tumor activity of curcumol, the mechanisms and signaling path against cancer are still unclear and no studies have investigated how curcumol induces colorectal cancer cell death in vivo.


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 proliferation of human colorectal cancer cell. (a) Dose- and time-dependent inhibition effect of cucumol on LoVo cells was evaluated by MTT assay; and (b) Dose- and time-dependent inhibition effect of cucumol on SW 480 cells was evaluated by MTT assay. Data represent mean ± SD from at least three independent experiments. *p < 0.05 when compared with the untreated control group.
© Copyright Policy
Related In: Results  -  Collection

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

ijms-16-19851-f001: Curcumol inhibited proliferation of human colorectal cancer cell. (a) Dose- and time-dependent inhibition effect of cucumol on LoVo cells was evaluated by MTT assay; and (b) Dose- and time-dependent inhibition effect of cucumol on SW 480 cells was evaluated by MTT assay. Data represent mean ± SD from at least three independent experiments. *p < 0.05 when compared with the untreated control group.
Mentions: In recent years, more and more cancer therapeutics on the market or in preclinical trails turn to natural products with low toxicity and drug resistance. Chinese people have used the medicinal plant Rhizoma Curcumae for thousands of years. Curcumol (Figure 1a) with the structure of a guaiane-type sesquiterpenoid hemiketal, has been reported to possess antitumor, antiproliferation, anti-inflammatory, anti-hepatic fibrosis, antioxidant, and antimicrobial activities with low cytotoxicity [6,7]. Recently, it has been reported that curcumol exhibited growth inhibitory and induced apoptosis activity in several human cancer cell lines in vitro, including cervical carcinoma, breast carcinoma, lung carcinoma, gastric carcinoma and hepatocarcinoma [8,9]. Chen found that 300 μM of curcumol could induce HSC-T6 apoptosis, while showing little toxicity to the normal liver cell line BRL-3A [10]. Tang found that curcumol (60 mg/kg) did not cause notable toxicity to the nude mouse [11]. Despite the increasing interest in the anti-tumor activity of curcumol, the mechanisms and signaling path against cancer are still unclear and no studies have investigated how curcumol induces colorectal cancer cell death in vivo.

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