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

Funding Information:

• First Affiliated Hospital of Chongqing Medical University's "Discipline Summit Plan" (China) (No. cyyy-xkdfjhcgzh-202303)
• Chongqing Young and Middle-aged Medical High-end Talent Studio (China) (No. cstc2022ycjh-bgzxm0103)
• China Postdoctoral Science Foundation (No. 2024MD754029)
• Chongqing Natural Science Foundation project (China) (No. CSTB2024NSCQ-MSX1218)

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Genes & Diseases publishes rigorously peer-reviewed and high quality original articles and authoritative reviews that focus on the molecular bases of human diseases. Emphasis is placed on hypothesis-driven, mechanistic studies relevant to pathogenesis and/or experimental therapeutics of human diseases. The journal has worldwide authorship, and a broad scope in basic and translational biomedical research of molecular biology, molecular genetics, and cell biology, including but not limited to cell proliferation and apoptosis, signal transduction, stem cell biology, developmental biology, gene regulation and epigenetics, cancer biology, immunity and infection, neuroscience, disease-specific animal models, gene and cell-based therapies, and regenerative medicine.

Scopus CiteScore: 8.4 | Impact Factor: 9.4

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