Bruceine D inhibits tumor growth and stem cell-like traits of osteosarcoma through inhibition of STAT3 signaling pathway.

Abstract

Patients with osteosarcoma exhibiting resistance to chemotherapy or presenting with metastasis usually have a poor prognosis. Osteosarcoma stem cells (OSCs) are a potential cause of tumor metastasis, relapse, and chemotherapy resistance. Therefore, it is necessary to develop novel therapeutic drugs, which not only kill osteosarcoma cells but also target OSCs. This study aims to explore the anti-osteosarcoma effects of Bruceine D (BD), a natural compound derived from Brucea javanica, and investigate its underlying mechanisms. Results demonstrated that BD could significantly inhibit cell proliferation and migration, induce cell cycle arrest, and promote apoptosis in osteosarcoma cells. Besides, BD could also suppress the sphere-forming and self-renewal ability of OSCs. Mechanistically, the inhibitory role of BD on osteosarcoma cell growth and migration including OSC stemness was partially executed through the inhibition of STAT3 signaling pathway. More importantly, BD showed significant anti-osteosarcoma activity without obvious side effects in vivo. Collectively, the results of this study demonstrated that BD exerts a strong inhibitory effect on tumor growth and stem cell like traits of osteosarcoma which may be partially due to STAT3 inhibition, suggesting that BD maybe a promising therapeutic candidate against osteosarcoma.

• Authors: Shangyu Wang, Hongzhi Hu, Binlong Zhong, Deyao Shi, Xiangcheng Qing, Cheng Cheng, Xiangyu Deng, Zhicai Zhang, Zengwu Shao
• Journal: Cancer medicine (Cancer Med) Vol. 8 Issue 17 Pg. 7345-7358 (12 2019) ISSN: 2045-7634 [Electronic] United States
• PMID: 31631559 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © 2019 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Chemical References

• Quassins
• STAT3 Transcription Factor
• STAT3 protein, human
• bruceine D

Topics

• Animals
• Apoptosis (drug effects)
• Bone Neoplasms (drug therapy)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Female
• Humans
• Mice
• Neoplastic Stem Cells (drug effects, pathology)
• Osteosarcoma (drug therapy, pathology)
• Quassins (pharmacology, therapeutic use)
• STAT3 Transcription Factor (metabolism)
• Signal Transduction (drug effects)
• Xenograft Model Antitumor Assays