Ke Weiwei, Wang Hongbo, Zhao Xiangxuan, Lu Zaiming
Department of Radiology, Shengjing Hospital of China Medical University, Shenyang 110004, LN, China.
Food Funct. 2021 Mar 1;12(4):1482-1497. doi: 10.1039/d0fo02243h.
Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. The prognosis of HCC is very poor due to the absence of symptoms and a lack of effective treatments. Studies have shown that various Foeniculum vulgare (fennel) extracts exhibit anti-cancer effects on malignant tumors such as skin cancer and prostate cancer. However, the anti-tumor activity of Foeniculum vulgare and its underlying molecular mechanisms towards HCC are unknown. Here, we provide fundamental evidence to show that the 75% ethanol extract of Foeniculum vulgare seeds (FVE) reduced cell viability, induced apoptosis, and effectively inhibited cell migration in HCC cells in vitro. HCC xenograft studies in nude mice showed that FVE significantly inhibited HCC growth in vivo. Mechanistic analyses showed that FVE reduced survivin protein levels and triggered mitochondrial toxicity, subsequently inducing caspase-3 activation and apoptosis. Survivin inhibition effectively sensitized HCC cells to FVE-induced apoptosis. Moreover, FVE did not induce a decrease in survivin or apoptotic toxicity in normal liver cells. Collectively, in vivo and in vitro results suggest that FVE exerts inhibitory effects in HCC by targeting the oncoprotein survivin, suggesting FVE may be a potential anti-cancer agent that may benefit patients with HCC.
肝细胞癌（HCC）是最常见的恶性肿瘤之一。由于无症状且缺乏有效治疗方法，HCC的预后非常差。研究表明，各种小茴香提取物对皮肤癌和前列腺癌等恶性肿瘤具有抗癌作用。然而，小茴香的抗肿瘤活性及其对HCC的潜在分子机制尚不清楚。在此，我们提供了基本证据表明小茴香种子75%乙醇提取物（FVE）在体外可降低HCC细胞的活力、诱导细胞凋亡并有效抑制细胞迁移。在裸鼠中进行的HCC异种移植研究表明，FVE在体内显著抑制HCC生长。机制分析表明，FVE降低了生存素蛋白水平并引发线粒体毒性，随后诱导半胱天冬酶-3激活和细胞凋亡。抑制生存素可有效使HCC细胞对FVE诱导的细胞凋亡敏感。此外，FVE不会导致正常肝细胞中生存素减少或产生凋亡毒性。总体而言，体内和体外结果表明，FVE通过靶向癌蛋白生存素对HCC发挥抑制作用，提示FVE可能是一种潜在的抗癌药物，可能使HCC患者受益。
