Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute

Liu,Huiping; Li,Guoning; Zhang,Bin; Sun,Deqing; Wu,Jing; Chen,Fang; Kong,Feng; Luan,Yun; Jiang,Wen; Wang,Rongmei; Xue,Xia

doi:10.3892/mmr.2018.8617

Suppression of the NF‑κB signaling pathway in colon cancer cells by the natural compound Riccardin D from Dumortierahirsute

Authors:
- Huiping Liu
- Guoning Li
- Bin Zhang
- Deqing Sun
- Jing Wu
- Fang Chen
- Feng Kong
- Yun Luan
- Wen Jiang
- Rongmei Wang
- Xia Xue
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Affiliations: Shandong Luye Pharmaceutical Co., Ltd., Yantai, Shandong 264000, P.R. China, Department of Pharmacy, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China, Central Laboratory, The Second Hospital of Shandong University, Jinan, Shandong 250033, P.R. China
Published online on: February 16, 2018 https://doi.org/10.3892/mmr.2018.8617
Pages: 5837-5843
Copyright: © Liu et al. This is an open access article distributed under the terms of Creative Commons Attribution License.

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Abstract

Colorectal cancer (CRC) is a major cause of mortality and morbidity. Chronic inflammation is closely associated with the development, progression and prognosis of the majority of intestinal malignancies. In recent years, targeting the nuclear factor (NF)‑κB signaling pathway for CRC therapy has become an attractive strategy. Riccardin D, a novel macrocyclicbis (bibenzyl) compound, was isolated from the Chinese liverwort plant. Previous studies have suggested that Riccardin D exerted chemo‑preventative effects against the intestinal malignancy formation. In the present study, cell counting kit‑8, Hochest 33258 staining, mitochondria membrane permeability assay, western blotting analysis, reverse transcription‑polymerase chain reaction, luciferase reporter gene assay and molecular modeling analysis were performed to detect the effect and mechanisms of Riccardin D on human colon cancer cells. The results demonstrated that Riccardin D significantly inhibited the growth of HT‑29 cells. In addition, the cDNA expression of cyclooxygenase‑2, and the protein expression and activity of NF‑κB and tumor necrosis factor‑α were downregulated; however, the protein expression of cleaved caspase‑3 and ‑9, and cleaved poly (adenosine diphosphate‑ribose) polymerase, and the B‑cell lymphoma (Bcl)‑2: Bcl‑2‑associated X protein ratio were upregulated. Furthermore, Auto Dock analysis identified binding sites between Riccardin D and NF‑κB. These results indicated that Riccardin D may inhibit cell proliferation and induce apoptosis in HT‑29 cells, which may be associated with the blocking of the NF‑κB signaling pathway. Thus, Riccardin D should be investigated as an NF‑κB inhibitor in cancer therapy.

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