6,8-Diprenylorobol is a natural compound mainly found in Glycyrrhiza uralensis fisch and Maclura tricuspidata, which has been used traditionally as food and medicine in Asia. So far, the antiproliferative effect of 6,8-diprenylorobol has not been studied yet in colon cancer. In this study, we aimed to evaluate the antiproliferative effects of 6,8-diprenylorobol in LoVo and HCT15, two kinds of human colon cancer cells. 6,8-Diprenylorobol inhibited the proliferation of LoVo and HCT15 cells in a dose- and time-dependent manner. A 40 μM of 6,8-diprenylorobol for 72 h reduced both of cell viability under 50%. After treatment of 6,8-diprenylorobol (40 and 60 μM) for 72 h, late apoptotic cell portion in LoVo and HCT15 cells were 24, 70% and 13, 90%, respectively, which was confirmed by checking DNA fragmentation in both cells. Mechanistically, 6,8-diprenylorobol activated p53 and its phosphorylated form (Ser15, Ser20, and Ser46) expression but suppressed Akt and mitogen-activated protein kinases (MAPKs) phosphorylation in LoVo and HCT15 cells. Interestingly, 6,8-diprenylorobol induced the generation of intracellular reactive oxygen species (ROS), which was attenuated with N-acetyl cysteine (NAC) treatment. Compared to the control, 60 μM of 6,8-diprenylorobol caused to increase ROS level to 210% in LoVo and HCT15, which was reduced into 161% and 124%, respectively with NAC. Furthermore, cell viability and apoptotic cell portion by 6,8-diprenylorobol was recovered by incubation with NAC. Taken together, these results indicate that 6,8-diprenylorobol has the potential antiproliferative effect against LoVo and HCT15 colon cancer cells through activation of p53 and generation of ROS.

中文翻译：

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6, 8-Diprenylorobol 通过激活细胞内活性氧和 p53 诱导人结肠癌细胞凋亡

6,8-Diprenylorobol 是一种天然化合物，主要存在于 Glycyrrhiza uralensis fisch 和 Maclura tricuspidata，在亚洲传统上被用作食品和药物。到目前为止，尚未研究 6,8-diprenylorobol 在结肠癌中的抗增殖作用。在这项研究中，我们旨在评估 6,8-diprenylorobol 对 LoVo 和 HCT15 这两种人类结肠癌细胞的抗增殖作用。6,8-Diprenylorobol 以剂量和时间依赖性方式抑制 LoVo 和 HCT15 细胞的增殖。40 μM 的 6,8-diprenylorobol 72 小时将两种细胞活力降低到 50% 以下。在 6,8-diprenylorobol（40 和 60 μM）处理 72 小时后，LoVo 和 HCT15 细胞中的晚期凋亡细胞部分分别为 24, 70% 和 13, 90%，这通过检查两种细胞中的 DNA 片段化得到证实. 机械上，6，8-diprenylorobol 激活 p53 及其磷酸化形式（Ser15、Ser20 和 Ser46）表达，但抑制 LoVo 和 HCT15 细胞中的 Akt 和丝裂原活化蛋白激酶 (MAPK) 磷酸化。有趣的是，6,8-diprenylorobol 诱导了细胞内活性氧 (ROS) 的产生，其通过 N-乙酰半胱氨酸 (NAC) 处理减弱。与对照相比，60 μM 6,8-diprenylorobol 导致 LoVo 和 HCT15 中 ROS 水平增加至 210%，而使用 NAC 分别降低至 161% 和 124%。此外，6,8-diprenylorobol 引起的细胞活力和细胞凋亡部分通过与 NAC 孵育而恢复。总之，这些结果表明 6,8-diprenylorobol 通过激活 p53 和生成 ROS 对 LoVo 和 HCT15 结肠癌细胞具有潜在的抗增殖作用。