Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE2 synthesis and COX-2 expression

Li,Ming; Tan,Shi-Yun; Wang,Xiao-Fan

doi:10.3892/or.2014.3543

December-2014 Volume 32 Issue 6

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December-2014 Volume 32 Issue 6

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Article

Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE2 synthesis and COX-2 expression

Authors:
- Ming Li
- Shi-Yun Tan
- Xiao-Fan Wang
View Affiliations / Copyright

Affiliations: Department of Gastroenterology, Renmin Hospital of Wuhan University, Wuhan, Hubei 430060, P.R. China
Pages: 2845-2853
|
Published online on: October 13, 2014

https://doi.org/10.3892/or.2014.3543
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Abstract

Cyclooxygenase-2 (COX-2) and its metabolite prostaglandin E2 (PGE2) can potentially affect most of the events in cancer development, including promotion of proliferation, resistance to apoptosis, angiogenesis, immune suppression and invasion. However, worldwide attention has predominantly centered on the cardiovascular toxicity of selective COX-2 inhibitors. Paeonol is a major active extract from the root bark of Paeonia suffruticosa Andrews with anti‑inflammatory, anti-oxidant, anti-allergic, anti-oxidation and antitumor effects. In the present study, we investigated the underlying mechanisms of paeonol in inducing apoptosis and aimed to ascertain whether its antitumor effect is associated with a reduction in COX-2 expression and a decrease in the levels of PGE2 in colorectal cancer cells. We observed that paeonol inhibited cell proliferation and induced apoptosis in a dose- and time-dependent manner in colorectal cancer cells, which was associated with a reduction in COX-2 expression and PGE2 synthesis. Treatment with the selective COX-2 inhibitor, celecoxib, or transient transfection of colorectal cancer cells with COX-2 siRNA, also inhibited cell proliferation and induced apoptosis. Western blot analysis showed that paeonol inhibited the activation of NF-κB, an upstream regulator of COX-2, and its translocation to the nucleus. Treatment with increasing doses of paeonol led to increased expression of pro-apoptotic factor Bax and decreased expression of anti-apoptotic factor Bcl-2. Caspase-3 and caspase-9 were activated, and paeonol induced loss of mitochondrial membrane potential, suggesting that the apoptosis induced by paeonol was mediated by mitochondrial pathways. In addition, paeonol significantly suppressed tumor growth in a xenograft tumor mouse model in a dose-dependent manner. Our findings indicate that paeonol exerts an antitumor effect on human colorectal cancer cells by inhibiting PGE2 production and COX-2 expression. We expect that paeonol may replace selective COX-2 inhibitors due to their toxic effects, and may offer a new strategy for the therapy of colorectal cancer.

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Journals

International Journal of Molecular Medicine

International Journal of Oncology

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Oncology Reports

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Oncology Letters

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Molecular and Clinical Oncology

World Academy of Sciences Journal

International Journal of Functional Nutrition

International Journal of Epigenetics

Medicine International

Paeonol exerts an anticancer effect on human colorectal cancer cells through inhibition of PGE2 synthesis and COX-2 expression

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