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Abstract：
Colon cancer is a common gastrointestinal malignancy that ranks third in incidence among gastrointestinal cancers. Therefore, screening bioactive compounds for treatment of colon cancer is urgently needed. Sanguisorba officinalis L. (SO) has been demonstrated that the extractions or monomers possess potential anti-tumor effect. In this study, we firstly used cell membrane chromatography (CMC) and ultra-performance liquid chromatography coupled with (quadrupole) time-of-flight mass spectrometry (UHPLC-(Q) TOF-MS/MS) to identify a novel active ingredient, octyl gallate (OG), from SO methanol extract (SO-MtOH). HCT116 and SW620 cells lines were used for in vitro research, which showed OG presents great anti-colon cancer effect by inhibiting proliferation, inducing apoptosis, and repressing the migration and invasion. Furthermore, SW620 bearing athymic nude mice was used to investigate the potential antitumor activity in vivo, which exhibited OG treatment remarkably lessened the tumor volume. Mechanism studies showed that OG downregulated the PI3K/AKT/mTOR signaling axis and induced apoptosis by upregulating the Bax/Bcl-2 protein and the cleaved caspase-3, caspase-9. In conclusion, our research innovatively applied the method of CMC to intriguingly unearth the potential anti-colon cancer ingredient OG and demonstrated its the great antineoplastic activity, which provide a new insight for researchers efficiently developing the novel apoptosis-inducing compound for colon cancer therapy.
摘要：
结肠癌是一种常见的胃肠道恶性肿瘤，发病率在胃肠道癌症中排名第三。因此,迫切需要筛选用于治疗结肠癌的生物活性化合物。已经证明，提取物或单体具有潜在的抗肿瘤作用。在这项研究中,我们首先使用细胞膜色谱（CMC）和超高效液相色谱-（四极杆）飞行时间质谱（UHPLC-（Q）TOF-MS/MS）鉴定了一种新的活性成分，没食子酸辛酯(OG),从SO甲醇提取物（SO-MtOH）。HCT116和SW620细胞系用于体外研究，这表明OG通过抑制增殖表现出抗结肠癌的作用，诱导细胞凋亡，压制移民和入侵。此外，携带SW620的无胸腺裸鼠用于研究体内潜在的抗肿瘤活性，表现出OG治疗显着减小了肿瘤体积。机制研究表明，OG下调PI3K/AKT/mTOR信号轴，并通过上调Bax/Bcl-2蛋白和裂解的caspase-3，caspase-9诱导细胞凋亡。总之,我们的研究创新性地应用了CMC的方法来有趣地发掘潜在的抗结肠癌成分OG，并证明了其巨大的抗肿瘤活性，这为研究人员有效开发用于结肠癌治疗的新型凋亡诱导化合物提供了新的见解。
