Veratramine: A potential candidate against osteosarcoma
Veratramine exhibits an anti-osteosarcoma effect by regulating PI3K/AKT signaling
image: (A) Schematic illustration of the in vivo anti-tumor effects of VER in BALB/c nude mice. (B) The body weight of nude mice. (C) The in vivo fluorescence images of 143B-fluc tumor-bearing mice treated with different drug groups on day 21. (D) Statistical analysis of relative fluorescence intensity. (E) The representative photo of tumors. (F) The effects of VER on tumor volume. (G) The effects of VER on tumors, lungs, heart, liver, spleen, and kidneys were detected by hematoxylin-eosin staining. (H) PCNA, Bcl-2, vimentin, MMP-2, p-PI3K, and p-AKT were detected by immunohistochemistry. Statistical significance is indicated by *P < 0.05 and **P < 0.01 versus the control group.
Credit: Zhou Xie, Xiao Qu, Ziyun Li, Yingtao Duan, Yafei Zhu, Jiayu Wang, Xueqian Han, Jun Zhang, Jinyong Luo, Xiaoji Luo
Osteosarcoma (OS) is a common bone malignancy that primarily affects adolescents and young adults and has an early propensity for metastasis. Given that current chemotherapeutic approaches cause significant side effects, and research into personalized treatment strategies is still in the early stages, there is a pressing need to develop new, safe, and effective drugs against OS.
Due to their low toxicity and potent efficacy, naturally occurring phytochemicals are increasingly considered for anti-tumor chemotherapeutic applications. In a recent study published in the Genes & Diseases journal, researchers at Chongqing Medical University and Chongqing Medical and Pharmaceutical College investigated the anti-tumor effects of veratramine (VER), an alkaloid derived from the American lily plant, against OS.
Initial in vitro experiments revealed that VER suppressed the proliferation, colony formation, migration, and invasion of human OS cells (143B and HOS). Additionally, VER induced G0-G1 phase cell cycle arrest and triggered apoptosis of the OS cells.
Network pharmacology analysis identified seven protein targets of VER: AKT1, CCND1, EGFR, BCL2, JAK2, HSP90AA1, and PI3KCA, which demonstrates its multi-target pharmacological effects and involvement in various signaling cascades against OS. Furthermore, molecular docking analysis showed that VER exerts its anti-OS effect by binding tightly to the core proteins of the PI3K/AKT signaling cascade, thereby inhibiting it. These findings were further validated in vitro.
In vivo experiments involving immunocompetent mice established that VER has an excellent safety profile and, therefore, could be considered for future experimental trials in other OS animal models. The authors further corroborated the therapeutic potential of VER in vivo, showing that VER inhibited the growth of OS and mitigated lung metastasis.
In conclusion, the findings of this study demonstrate that VER inhibits the proliferation, migration, and invasion of OS cells, and induces apoptosis and cell cycle arrest, both in vitro and in vivo. Moreover, VER has an excellent safety profile, making it a promising candidate against OS.
Reference
Title of the original paper: Veratramine influences the proliferation of human osteosarcoma cells through modulation of the PI3K/AKT signaling cascade
Journal: Genes & Diseases
Genes & Diseases is a journal for molecular and translational medicine. The journal primarily focuses on publishing investigations on the molecular bases and experimental therapeutics of human diseases. Publication formats include full length research article, review article, short communication, correspondence, perspectives, commentary, views on news, and research watch
DOI: https://doi.org/10.1016/j.gendis.2025.101630
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