Chen Tzu-Hua, Chang Chi-Chang, Houng Jer-Yiing, Chang Tzu-Hsien, Chen Ya-Ling, Hsu Chia-Chang, Chang Long-Sen
Institute of Biomedical Sciences, National Sun Yat-Sen University, Kaohsiung 80420, Taiwan.
Department of Nutritional Therapy, Kaohsiung Chang Gung Memorial Hospital, Kaohsiung 83340, Taiwan.
Pharmaceuticals (Basel). 2022 Jul 3;15(7):826. doi: 10.3390/ph15070826.
Previous studies have demonstrated that (SO) has a suppressive effect on the growth and migration of endometrial and cervical cancer cells. The present study examined the effect of SO ethanolic extract (SOE) on the proliferation and migration of hepatocellular carcinoma (HCC) and examined the effects of SOE on non-cancerous cells using HaCaT keratinocytes as a model. The SOE effectively inhibited the proliferation of Hepa1-6 (IC = 282.4 μg/mL) and HepG2 (IC = 344.3 μg/mL) hepatoma cells, whereas it has less cytotoxic effect on HaCaT cells (IC = 892.4 μg/mL). The SOE treatment increased the generation of ROS in HCC, but decreased the expression of antioxidant enzymes such as superoxide dismutase, glutathione peroxidase and catalase. In contrast, it reduced intracellular ROS formation and upregulated the expression of the related antioxidant enzymes in the HO-stimulated HaCaT cells. The SOE intervention also down-regulated the anti-apoptotic Bcl-2 and the migration-related proteins including matrix metalloproteinases (MMPs) and β-catenin in the HCC, suggesting that SOE could promote HCC apoptosis and inhibit HCC migration. On the contrary, it reduced apoptosis and promoted the migration of the keratinocytes. Additionally, the SOE treatment significantly up-regulated the pro-inflammatory cytokines, including TNF-α, IL-6 and IL-1β, in Hepa1-6 and HepG2 cells. Conversely, it significantly decreased the expression of these cytokines in the HO-induced HaCaT cells. These findings indicated that SOE treatment can delay the progression of HCC by increasing oxidative stress, promoting inflammatory response, inducing cancer cell apoptosis and inhibiting their migration. It also has protective effects from pro-oxidant HO in non-cancerous cells. Therefore, SOE may provide a potential treatment for liver cancer.
先前的研究表明，（SO）对子宫内膜癌和子宫颈癌细胞的生长和迁移具有抑制作用。本研究检测了SO乙醇提取物（SOE）对肝癌（HCC）细胞增殖和迁移的影响，并以HaCaT角质形成细胞为模型检测了SOE对非癌细胞的影响。SOE有效抑制了Hepa1-6（IC = 282.4μg/mL）和HepG2（IC = 344.3μg/mL）肝癌细胞的增殖，而对HaCaT细胞的细胞毒性作用较小（IC = 892.4μg/mL）。SOE处理增加了HCC中活性氧（ROS）的生成，但降低了超氧化物歧化酶、谷胱甘肽过氧化物酶和过氧化氢酶等抗氧化酶的表达。相反，它减少了HO刺激的HaCaT细胞内ROS的形成，并上调了相关抗氧化酶的表达。SOE干预还下调了HCC中抗凋亡蛋白Bcl-2以及包括基质金属蛋白酶（MMPs）和β-连环蛋白在内的迁移相关蛋白，表明SOE可促进HCC细胞凋亡并抑制其迁移。相反，它减少了角质形成细胞的凋亡并促进其迁移。此外，SOE处理显著上调了Hepa1-6和HepG2细胞中促炎细胞因子，包括肿瘤坏死因子-α、白细胞介素-6和白细胞介素-1β的表达。相反，它显著降低了HO诱导的HaCaT细胞中这些细胞因子的表达。这些发现表明，SOE处理可通过增加氧化应激、促进炎症反应、诱导癌细胞凋亡和抑制其迁移来延缓HCC的进展。它对非癌细胞中的促氧化剂HO也有保护作用。因此，SOE可能为肝癌提供一种潜在的治疗方法。
