2. Academic Validation
  3. Triptolidenol, isolated from Tripterygium wilfordii, disrupted NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKβ in clear cell renal cell carcinoma

Triptolidenol, isolated from Tripterygium wilfordii, disrupted NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKβ in clear cell renal cell carcinoma

  • Fitoterapia. 2021 Jan:148:104779. doi: 10.1016/j.fitote.2020.104779.
Junmei Jin 1,  Meirong Zhou 1,  Xun Wang 2,  Min Liu 3,  Huilian Huang 4,  Fei Yan 4,  Zhenlong Yu 5,  Xiaohong Shu 2,  Xiaokui Huo 2,  Lei Feng 2,  Baojing Zhang 2,  Shanshan Huang 2,  Sa Deng 2,  Chao Wang 6,  Xiaochi Ma 4
Affiliations

Affiliations

  • 1 Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China; Academy of Integrative Medicine, College of Pharmacy, Dalian Medical University, The Third People's Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian 116044, China.
  • 2 Academy of Integrative Medicine, College of Pharmacy, Dalian Medical University, The Third People's Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian 116044, China.
  • 3 Academy of Integrative Medicine, College of Pharmacy, Dalian Medical University, The Third People's Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian 116044, China; Neurology Department, Dalian University Affiliated Xinhua Hospital, Dalian 116021, China.
  • 4 Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China.
  • 5 Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China; Academy of Integrative Medicine, College of Pharmacy, Dalian Medical University, The Third People's Hospital of Dalian, Non-Directly Affiliated Hospital of Dalian Medical University, Dalian 116044, China. Electronic address: qdyuzl871123@163.com.
  • 6 Laboratory of Modern Preparation of TCM, Ministry of Education, Jiangxi University of Traditional Chinese Medicine, Nanchang 330004, China. Electronic address: wach_edu@sina.com.
PMID: 33242535 DOI: 10.1016/j.fitote.2020.104779
Abstract

Triptolidenol (TPD) is an epoxy diterpene lactone from Tripterygium wilfordii, which has been used for chronic nephritis in China，and possessed various pharmacological properties, such as anti-inflammatory and anti-cancer activities. However, the precise molecular antitumor mechanism of TPD remains to be elucidated. In this study, we investigated the effects of TPD on human clear cell renal cell carcinoma (ccRCC) and investigated its precise anti-tumor mechanisms. It was showed that TPD significantly suppressed ccRCC cell proliferation, cell migration, and induced cell cycle arrest at S phase. Furthermore, TPD also induced Apoptosis by activating the cytochrome c (cyt c)/Caspase cascade signaling pathway. Moreover, using confocal immunofluorescence, a dual-luciferase reporter assay and molecular docking study, the results showed that TPD obviously reduced the expression of COX-2 by inhibiting the kinase activity of IKKβ via targeting its ATP-binding domain, and then attenuating the transactivation of NF-κB. Collectively, our study demonstrated that TPD suppressed renal cell carcinoma growth through disrupting NF-κB/COX-2 pathway by targeting ATP-binding sites of IKKβ, and provided pharmacological evidence that TPD exhibits potential use in the treatment of COX-2-mediated diseases such as ccRCC.

Keywords

COX-2; Clear cell renal cell carcinoma; IKKβ; NF- κB; Triptolidenol.

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