Trinh Nguyet-Tran, Nguyen Thi Minh Ngoc, Yook Jong-In, Ahn Sang-Gun, Kim Soo-A
Department of Biochemistry, Dongguk University College of Oriental Medicine, Gyeongju 38066, Korea.
Department of Oral Pathology, Yonsei University College of Dentistry, Seoul 03722, Korea.
Pharmaceuticals (Basel). 2022 Mar 17;15(3):364. doi: 10.3390/ph15030364.
Considering the high metastatic potential of colorectal cancer (CRC), the inhibition of metastasis is important for anti-CRC therapy. Ledeb () is a perennial herbaceous plant that is widely distributed in Asia. The extracts of have shown diverse pharmacological properties, such as antimicrobial, anti-inflammatory, and antitumor activities. In the present study, the antimetastatic activity of was evaluated. Methanol extraction from the roots of was performed by high-performance liquid chromatography (HPLC) and 12 fractions were obtained. Among these, fraction 4 showed the most potent inhibitory effect on the migration of colon cancer cells. Using LC-HR MS analysis, quercetin and quercitrin were identified as flavonoids contained in fraction 4. Like fraction 4, quercetin and quercitrin effectively inhibited the migration and invasion of RKO cells. While the level of E-cadherin was increased, the levels of N-cadherin and vimentin were decreased by the same agents. Although they all activate the p38, JNK, and ERK signaling pathways, only SP600125, an inhibitor of the JNK pathway, specifically inhibited the effect of fraction 4, quercetin, and quercitrin on cell migration. An in vivo experiment also confirmed the antitumor activity of quercetin and quercitrin. Collectively, these results suggest that and its two flavonoids, quercetin and quercitrin, are candidates for the antimetastatic treatment of CRC.
鉴于结直肠癌（CRC）具有较高的转移潜能，抑制转移对于抗CRC治疗至关重要。Ledeb（）是一种多年生草本植物，广泛分布于亚洲。其提取物已显示出多种药理特性，如抗菌、抗炎和抗肿瘤活性。在本研究中，对Ledeb的抗转移活性进行了评估。通过高效液相色谱（HPLC）从Ledeb的根中进行甲醇提取，得到了12个馏分。其中，馏分4对结肠癌细胞的迁移显示出最有效的抑制作用。使用液相色谱-高分辨质谱（LC-HR MS）分析，槲皮素和槲皮苷被鉴定为馏分4中所含的黄酮类化合物。与馏分4一样，槲皮素和槲皮苷有效地抑制了RKO细胞的迁移和侵袭。这些物质使E-钙黏蛋白水平升高，同时降低了N-钙黏蛋白和波形蛋白的水平。尽管它们都激活了p38、JNK和ERK信号通路，但只有JNK通路抑制剂SP600125特异性地抑制了馏分4、槲皮素和槲皮苷对细胞迁移的作用。体内实验也证实了槲皮素和槲皮苷的抗肿瘤活性。总的来说，这些结果表明Ledeb及其两种黄酮类化合物槲皮素和槲皮苷是CRC抗转移治疗的候选药物。
