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.
Mol Med Rep. 2018 Apr;17(4):5837-5843. doi: 10.3892/mmr.2018.8617. Epub 2018 Feb 16.
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.
结直肠癌（CRC）是导致死亡率和发病率的主要原因。慢性炎症与大多数肠道恶性肿瘤的发展、进展和预后密切相关。近年来，针对核因子（NF）-κB 信号通路治疗 CRC 已成为一种有吸引力的策略。Riccardin D 是一种从中国肝叶植物中分离得到的新型大环双（联苄基）化合物。先前的研究表明 Riccardin D 对肠道恶性肿瘤的形成具有化学预防作用。在本研究中，通过细胞计数试剂盒-8、Hochest 33258 染色、线粒体膜通透性测定、Western blot 分析、逆转录-聚合酶链反应、荧光素酶报告基因分析和分子建模分析，检测 Riccardin D 对人结肠癌细胞的作用及其机制。结果表明 Riccardin D 可显著抑制 HT-29 细胞的生长。此外，环氧化酶-2 的 cDNA 表达、NF-κB 和肿瘤坏死因子-α的蛋白表达和活性下调，而 cleaved caspase-3 和 -9 以及 cleaved 多聚（腺苷二磷酸核糖）聚合酶和 B 细胞淋巴瘤（Bcl）-2：Bcl-2 相关 X 蛋白的比值上调。此外，Auto Dock 分析确定了 Riccardin D 与 NF-κB 之间的结合位点。这些结果表明 Riccardin D 可能通过抑制 NF-κB 信号通路来抑制 HT-29 细胞的增殖并诱导其凋亡。因此，Riccardin D 可作为癌症治疗中的 NF-κB 抑制剂进行研究。
