Resveratrol, a phytoalexin present in grapes and other edible foods, has been reported to have beneficial effects against various diseases including cancer. We previously reported that resveratrol and its derivative, caffeic acid-adducted resveratrol, selectively inhibit the three-dimensional (3D) proliferation of a human colorectal cancer cell line, HCT116 with activating KRAS mutation. Herein, we demonstrated that a novel compound, ferulic acid-bound resveratrol, also represses the 3D proliferation of HCT116 cells. We observed that resveratrol conjugated to two ferulic acids represses the 3D proliferation of HCT116 cells more strongly than resveratrol and resveratrol conjugated to one ferulic acid. Resveratrol conjugated to two ferulic acids also inhibited the 3D proliferation of MCF7 human breast cancer cells. We further uncovered that the resveratrol derivative increases the mRNA level of the tumor suppressor p15, a CDK inhibitor that functions as a brake of cell proliferation in HCT116 cells. These results imply that the resveratrol derivative represses 3D proliferation via increasing p15 expression in HCT116 cells.

中文翻译：

---

一种新型化合物阿魏酸结合白藜芦醇可诱导肿瘤抑制基因 p15 并抑制结直肠癌细胞的三维增殖。

白藜芦醇是一种存在于葡萄和其他可食用食品中的植物抗毒素，据报道对包括癌症在内的多种疾病具有有益作用。我们之前报道过白藜芦醇及其衍生物咖啡酸加合物白藜芦醇选择性地抑制人结直肠癌细胞系 HCT116 的三维 (3D) 增殖并激活 KRAS 突变。在这里，我们证明了一种新化合物阿魏酸结合的白藜芦醇也抑制了 HCT116 细胞的 3D 增殖。我们观察到与两种阿魏酸结合的白藜芦醇比与一种阿魏酸结合的白藜芦醇和白藜芦醇更强烈地抑制 HCT116 细胞的 3D 增殖。与两种阿魏酸结合的白藜芦醇还抑制 MCF7 人乳腺癌细胞的 3D 增殖。我们进一步发现白藜芦醇衍生物增加了肿瘤抑制因子 p15 的 mRNA 水平，p15 是一种 CDK 抑制剂，可作为 HCT116 细胞中细胞增殖的制动器。这些结果表明白藜芦醇衍生物通过增加 HCT116 细胞中 p15 的表达来抑制 3D 增殖。