KHU-KIST Department of Converging Science and Technology, Kyung Hee University, Seoul, South Korea.
Department of Science in Korean Medicine, Kyung Hee University, Seoul, South Korea.
Phytother Res. 2021 Jul;35(7):3875-3885. doi: 10.1002/ptr.7095. Epub 2021 Apr 1.
Brassinin (BSN), a precursor of phytoalexins, extracted from Chinese cabbage has been reported to act as a promising anti-neoplastic agent. However, the effects of BSN on colon cancer cells and its underlying mechanisms have not been fully elucidated. This study aimed at investigating the anti-neoplastic impact of BSN and its possible synergistic effect with paclitaxel on colon cancer cells. The effect of BSN on Janus-activated kinases (JAKs)/signal transducer and activator of transcription 3 (STAT3) and phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt)/mammalian target of rapamycin (mTOR) signaling pathways and its downstream functions was deciphered using diverse assays in colon carcinoma cells. We found that BSN displayed significant cytotoxic effect and suppressed cell proliferation on colon carcinoma cells. Additionally, it was noted that BSN modulated oncogenic gene expression and induced apoptosis through down regulating multiple oncogenic signaling cascades such as JAKs/STAT3 and PI3K/Akt/mTOR simultaneously. Besides, BSN-paclitaxel combination significantly increased cytotoxicity and induced apoptosis synergistically as compared with individual treatment of both the agents. Overall, our findings indicate that BSN may be a novel candidate for anti-colon cancer targeted therapy.
吲哚-3-甲醇（BSN）是植物抗毒素的前体，从白菜中提取出来，被报道具有很有前途的抗肿瘤作用。然而，BSN 对结肠癌细胞的作用及其潜在的协同作用与紫杉醇对结肠癌细胞的影响尚未完全阐明。本研究旨在探讨 BSN 的抗肿瘤作用及其与紫杉醇联合应用对结肠癌细胞的可能协同作用。通过在结肠癌细胞中进行多种实验，解析了 BSN 对 Janus 激活激酶（JAKs）/信号转导和转录激活因子 3（STAT3）和磷脂酰肌醇 3-激酶（PI3K）/蛋白激酶 B（Akt）/哺乳动物雷帕霉素靶蛋白（mTOR）信号通路及其下游功能的影响。结果表明，BSN 对结肠癌细胞表现出显著的细胞毒性作用和抑制增殖作用。此外，还注意到 BSN 通过同时下调多个致癌信号级联，如 JAKs/STAT3 和 PI3K/Akt/mTOR，调节致癌基因表达并诱导细胞凋亡。此外，BSN-紫杉醇联合用药与两种药物单独用药相比，显著增加了细胞毒性并协同诱导细胞凋亡。综上所述，我们的研究结果表明，BSN 可能是一种新型的结肠癌靶向治疗候选药物。
