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Curcumin Induces Pyroptosis-Associated Molecular Changes in Osteosarcoma Cells Correlating with the
Keqing Yuan1,2, Xingyu Zhao3, Jiayi Guo3
1Jilin Provincial Technology Collaborative Innovation Center of Hypobaric Hypoxia, School of Basic Medical Sciences, Jilin Medical University, Jilin 132013, China.
Nutrients
|June 12, 2026
Summary
Curcumin triggers pyroptosis and apoptosis in osteosarcoma cells by activating the ROS/NLRP3/CASPASE-1/GSDMD pathway and inhibiting PI3K/AKT signaling, offering new therapeutic strategies against this bone cancer.
Area of Science:
- Oncology
- Molecular Biology
- Biochemistry
Background:
- Osteosarcoma is a prevalent bone cancer in children and adolescents, often exhibiting chemoresistance.
- Novel therapeutic approaches are crucial to combat osteosarcoma's aggressive nature and treatment resistance.
Purpose of the Study:
- To investigate curcumin's ability to induce pyroptosis in human osteosarcoma cells.
- To elucidate the molecular mechanisms underlying curcumin's effects, focusing on the ROS/NLRP3/CASPASE-1/GSDMD axis and PI3K/AKT pathway.
Main Methods:
- Human osteosarcoma cells (U2OS, MG63) were treated with curcumin.
- Assessed cell viability, pyroptotic morphology, LDH release, cytokine secretion (IL-1β/IL-18), mitochondrial potential, ROS levels, and protein expression (Western blotting).
- Pharmacological inhibition of caspases was employed for validation.
Main Results:
- Curcumin inhibited osteosarcoma cell proliferation and induced pyroptotic features.
- Curcumin increased LDH release, IL-1β/IL-18 secretion, and ROS accumulation.
- Curcumin upregulated NLRP3, CASPASE-1, GSDMD-N, and activated apoptosis (Bax, Bcl-2, CASPASE-3) while suppressing the PI3K/AKT pathway.
Conclusions:
- Curcumin induces both apoptosis and pyroptosis in osteosarcoma cells via the ROS/NLRP3/CASPASE-1/GSDMD axis and PI3K/AKT suppression.
- Caspase-dependent apoptosis contributes significantly to curcumin's anticancer effects.
- Targeting multiple cell death pathways presents a promising strategy against osteosarcoma resistance.
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