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

Peng,Lei; Liu,An; Shen,Yue; Xu,Hua-Zi; Yang,Shi-Zhou; Ying,Xiao-Zhou; Liao,Wei; Liu,Hai-Xiao; Lin,Zhong-Qin; Chen,Qing-Yu; Cheng,Shao-Wen; Shen,Wei-Dong

doi:10.3892/or.2012.2165

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

Authors:
- Lei Peng
- An Liu
- Yue Shen
- Hua-Zi Xu
- Shi-Zhou Yang
- Xiao-Zhou Ying
- Wei Liao
- Hai-Xiao Liu
- Zhong-Qin Lin
- Qing-Yu Chen
- Shao-Wen Cheng
- Wei-Dong Shen
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Affiliations: Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Orthopaedic Surgery, The First People's Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China, Department of Orthopaedic Surgery, The Second Affiliated Hospital of Wenzhou Medical College, Wenzhou, Zhejiang 325000, P.R. China, Department of Orthopaedic Surgery, Hospital of Integrated Traditional Chinese and Western Medicine of Wenzhou, Zhejiang 325000, P.R. China, Department of Orthopaedic Surgery, The First People's Hospital of Yueyang, Yueyang, Hunan 414000, P.R. China
Published online on: December 4, 2012 https://doi.org/10.3892/or.2012.2165
Pages: 571-578

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Abstract

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 downstream effector molecules is a possible underlying mechanism of the antitumor and anti-angiogenic activity of thymoquinone in osteosarcoma.

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