Suppressive Effects of Siegesbeckia orientalis Ethanolic Extract on Proliferation and Migration of Hepatocellular Carcinoma Cells through Promoting Oxidative Stress, Apoptosis and Inflammatory Responses

被引:5
作者
Chen, Tzu-Hua [1 ,2 ]
Chang, Chi-Chang [3 ,4 ]
Houng, Jer-Yiing [5 ,6 ]
Chang, Tzu-Hsien [4 ]
Chen, Ya-Ling [4 ]
Hsu, Chia-Chang [7 ,8 ,9 ]
Chang, Long-Sen [1 ]
机构
[1] Natl Sun Yat Sen Univ, Inst Biomed Sci, Kaohsiung 80420, Taiwan
[2] Kaohsiung Chang Gung Mem Hosp, Dept Nutr Therapy, Kaohsiung 83340, Taiwan
[3] I Shou Univ, Coll Med, Sch Med Int Students, Kaohsiung 82445, Taiwan
[4] E Da Dachang Hosp, Dept Obstet & Gynecol, E Da Hosp, Kaohsiung 82445, Taiwan
[5] I Shou Univ, Dept Nutr, Kaohsiung 82445, Taiwan
[6] I Shou Univ, Dept Chem Engn, Kaohsiung 82445, Taiwan
[7] I Shou Univ, Coll Med, Sch Chinese Med Postbaccalaureate, Kaohsiung 82445, Taiwan
[8] E Da Hosp, Dept Internal Med, Div Gastroenterol & Hepatol, Kaohsiung 82445, Taiwan
[9] E Da Dachang Hosp, Hlth Examinat Ctr, Kaohsiung 80794, Taiwan
关键词
Siegesbeckia orientalis; hepatocellular carcinoma; keratinocytes; proliferation and migration; oxidative stress; inflammatory response; NF-KAPPA-B; WNT/BETA-CATENIN; MATRIX METALLOPROTEINASES; RISK-FACTORS; IN-VITRO; CANCER; ACTIVATION; INVASION; ROLES; MODULATION;
D O I
10.3390/ph15070826
中图分类号
R914 [药物化学];
学科分类号
100701 ;
摘要
Previous studies have demonstrated that Siegesbeckia orientalis (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 (IC50 = 282.4 mu g/mL) and HepG2 (IC50 = 344.3 mu g/mL) hepatoma cells, whereas it has less cytotoxic effect on HaCaT cells (IC50 = 892.4 mu g/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 H2O2-stimulated HaCaT cells. The SOE intervention also down-regulated the anti-apoptotic Bcl-2 and the migration-related proteins including matrix metalloproteinases (MMPs) and beta-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-alpha, IL-6 and IL-1 beta, in Hepa1-6 and HepG2 cells. Conversely, it significantly decreased the expression of these cytokines in the H2O2-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 H2O2 in non-cancerous cells. Therefore, SOE may provide a potential treatment for liver cancer.
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页数:18
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