Andrographolide inhibits the growth of human osteosarcoma cells by suppressing Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways. (25th September 2022)

• Record Type: Journal Article
• Authors: Huang, Huakun; Lu, Qiuping; Yuan, Xiaohui; Zhang, Ping; Ye, Caihong; Wei, Mengqi; Yang, Chunmei; Zhang, Lulu; Huang, Yanran; Luo, Xiaoji; Luo, Jinyong
• Is Part Of: Chemico-biological interactions. Volume 365(2022)
• Publication Date: 2022-09-25
• Subjects: Andrographolide -- Osteosarcoma -- Wnt/β-catenin -- PI3K/AKT -- NF-κB; Biochemistry -- Periodicals; Toxicological chemistry -- Periodicals; Biochemistry -- Periodicals; Biologie moléculaire -- Périodiques; Biochimie -- Périodiques; Toxicologie biochimique -- Périodiques; 572
• DOI: 10.1016/j.cbi.2022.110068
• Languages: English
• ISSNs: 0009-2797

Abstract

Abstract: Osteosarcoma (OS) is an aggressive malignant skeletal tumor characterized by an extremely poor prognosis and a high tendency to recur. The frequently used anti-OS chemotherapy regents are often limited by drug resistance and severe adverse events. It is urgent to develop more effective, tolerable and safe drugs for the treatment of OS. Andrographolide (AG), a diterpenoid lactone isolated from Andrographis paniculata, has been proved to possess anti-tumor activity against several human cancer types. In this current study, we evaluated the inhibitory effect of AG on human OS cells and probed the possible mechanism. We found that AG inhibited the proliferation of human OS cells and blocked cell cycle at G2/M phase. Furthermore, AG impeded the migration and invasion, while promoted the apoptosis of human OS cells. Moreover, we found that AG inhibited OS growth and lung metastasis in orthotopic transplantation model. Mechanistically, we demonstrated that AG suppressed the activity of Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathways. Notably, we validated that AG synergized with the inhibitors of Wnt/β-catenin, PI3K/AKT and NF-κB to suppress the proliferation, migration and invasion of human OS cells. Collectively, our study conclusively demonstrates that AG inhibits the growth of human OS cells, thus, may be a promising candidate for the treatment of OS. Highlights: Andrographolide effectively inhibited osteosarcoma cell growth in vitro and in vivo. Andrographolide had relative lower toxicity against normal cells. Andrographolide suppressed Wnt/β-catenin, PI3K/AKT and NF-κB signaling pathway.