Natural products reshape osteosarcoma cell fate: promoting cell death.

Abstract

Osteosarcoma is the most prevalent primary malignant bone tumor in children and adolescents. Despite advancements in adjuvant chemotherapy and surgical techniques, the overall survival rate of osteosarcoma patients remains suboptimal, particularly in cases of metastatic or recurrent disease. Programmed cell death (PCD), a highly regulated process that includes apoptosis, autophagy, ferroptosis, pyroptosis, and necroptosis, plays a pivotal role in determining cellular fate (survival and death). In osteosarcoma, PCD dysregulation enables malignant cells to evade cell death signals, thereby accelerating tumor development. Natural products derived from various medicinal plants and dietary components exhibit promising potential for osteosarcoma treatment by regulating PCD through different mechanisms. With advantages such as low cost, minimal side effects, and wide availability, natural products have attracted considerable attention for translational research. This review systematically synthesizes current knowledge on PCD subtypes in osteosarcoma and elucidates the molecular mechanisms by which natural products regulate PCD to inhibit the development of osteosarcoma. By integrating these insights, we aim to offer novel perspectives for developing targeted therapeutic strategies and improving clinical outcomes in osteosarcoma patients.