Bruceantinol targeting STAT3 exerts promising antitumor effects in in vitro and in vivo osteosarcoma models.

Autor: Miao J; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Chen S; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Cao H; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Ding Z; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Li Y; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Wang W; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Nundlall K; Xiangya School of Medicine, Central South University, Changsha, Hunan, P. R. China., Deng Y; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China., Li J; Department of Spine Surgery, The Third Xiangya Hospital of Central South University, Changsha, Hunan, P. R. China.
Jazyk: angličtina
Zdroj: Molecular carcinogenesis [Mol Carcinog] 2024 Jun; Vol. 63 (6), pp. 1133-1145. Date of Electronic Publication: 2024 Mar 01.
DOI: 10.1002/mc.23714
Abstrakt: Bruceantinol (BOL) is a quassinoid compound found in the fruits of Brucea javanica. Previous research has highlighted the manifold physiological and pharmacological activities of BOL. Notably, BOL has demonstrated antitumor cytotoxic and antibacterial effects, lending support to its potential as a promising therapeutic agent for various diseases. Despite being recognized as a potent antitumor inhibitor in multiple cancer types, its efficacy against osteosarcoma (OS) has not been elucidated. In this work, we investigated the antitumor properties of BOL against OS. Our findings showed that BOL significantly decreased the proliferation and migration of OS cells, induced apoptosis, and caused cell death without affecting the cell cycle. We further confirmed that BOL potently suppressed tumor growth in vivo. Mechanismly, we discovered that BOL directly bound to STAT3, and prevent the activation of STAT3 signaling at low nanomolar concentrations. Overall, our study demonstrated that BOL potently inhibited the growth and metastasis of OS, and efficiently suppressed STAT3 signaling pathway. These results suggest that BOL could be a promising therapeutic candidate for OS.
(© 2024 Wiley Periodicals LLC.)
Databáze: MEDLINE
Externí odkaz: