Antitumor and anti-angiogenesis effects of thymoquinone on osteosarcoma through the NF-κB pathway

作者：Lei Peng, An Liu, Yue Shen, Huazi Xu, Shizhou Yang, Xiaozhou Ying, WEI LIAO, Hai-xiao Liu, Zhong-Qin Lin, Qingyu Chen, Shaowen Cheng, Weidong Shen · 发表于：Oncology Reports · 年份：2012 · DOI：10.3892/or.2012.2165 · 被引用次数：149 · 研究领域：Nigella sativa pharmacological applications、Natural Compounds in Disease Treatment、Bioactive Compounds and Antitumor Agents

Thymoquinone (TQ), the predominant bioactive constituent derived from the medicinal spice Nigella sativa (also known as black cumin), has been applied for medical purposes for more than 2,000 years. Recent studies reported that thymoquinone exhibited inhibitory effects on the cell proliferation of several cancer cell lines. This study was performed to investigate the antitumor and anti-angiogenic effects of thymoquinone on osteosarcoma in vitro and in vivo. Our results showed that thymoquinone induced a higher percentage of growth inhibition and apoptosis in the human osteosarcoma cell line SaOS-2 compared to that of control, and thymoquinone significantly blocked human umbilical vein endothelial cell (HUVEC) tube formation in a dose-dependent manner. To investigate the possible mechanisms involved in these events, we performed electrophoretic mobility shift assay (EMSA) and western blot analysis, and found that thymoquinone significantly downregulated NF-κB DNA-binding activity, XIAP, survivin and VEGF in SaOS-2 cells. Moreover, the expression of cleaved caspase-3 and Smac were upregulated in SaOS-2 cells after treatment with thymoquinone. In addition to these in vitro results, we also found that thymoquinone inhibits tumor angiogenesis and tumor growth through suppressing NF-κB and its regulated molecules. Collectively, our results demonstrate that thymoquinone effectively inhibits tumor growth and angiogenesis both in vitro and in vivo. Moreover, inhibition of NF-κB and do...