ArticleMedical oncology (Northwood, London, England)2023
Zoledronic acid induces ferroptosis by upregulating POR in osteosarcoma.
Article in Medical oncology (Northwood, London, England), 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 10 papers.
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Who cites it
10 citing papers in PubMed, 15 citations in OpenAlex.
- Lenvatinib induces ferroptosis-related changes in osteosarcoma cells involving the p-STAT3/p53/xCT axis.Frontiers in oncology · 2026Article
- Iron-Related Metabolic Targets in the Treatment of Osteosarcoma: Research Progress and Prospects.Biomedicines · 2025Review
- PSAT1 inhibits ferroptosis in osteosarcoma cells by activating the Xct/GPX4 signaling axis.Scientific reports · 2025Article
- Clinical and biochemical efficacy zoledronic acid and denosumab combination: focus serum inflammatory factor level (serum ifcs), bone gla protein (bgp), and bone turnover markers b-collagen degradation product (b-ctx), and procollagen type 1 n-terminal propeptide (p1np).Journal of medical biochemistry · 2025Article
- Ferroptosis and bone health: bridging the gap between mechanisms and therapy.Frontiers in immunology · 2025Review
- Harnessing ferroptosis for enhanced sarcoma treatment: mechanisms, progress and prospects.Experimental hematology & oncology · 2024Review
- Novel Insights on Ferroptosis Modulation as Potential Strategy for Cancer Treatment: When Nature Kills.Antioxidants & redox signaling · 2024Review
- Decoding ferroptosis: transforming orthopedic disease management.Frontiers in pharmacology · 2024Review
- Targeting Ferroptosis in Bone-Related Diseases: Facts and Perspectives.Journal of inflammation research · 2023Review
- Ferroptosis-related gene HIC1 in the prediction of the prognosis and immunotherapeutic efficacy with immunological activity.Frontiers in immunology · 2023Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Osteosarcoma, usually originating in the stroma, is the most common primary bone cancer in adolescents, and its prognosis is poor. Surgery, adjuvant and neoadjuvant chemotherapy and radiation therapy are not satisfactory at the present time. Therefore, it is critical to develop novel therapeutic strategies to improve the quality of life and long-term survival rate of osteosarcoma patients. In this study, we discovered that zoledronic acid (ZOL) dramatically increased cell death in osteosarcoma cells, and this cytotoxicity was greatly reversed by liproxstatin-1 (a ferroptosis inhibitor). ZOL also had an obvious effect on lipid peroxidation and reactive oxygen species (ROS), which suggested that ZOL most certainly induces ferroptosis in osteosarcoma cells. In addition, we further found that ZOL increases cytochrome P450 oxidoreductase (POR) expression dose dependently in osteosarcoma cell lines. Knockdown of POR attenuated ZOL-induced cytotoxicity and attenuated the effect of ferroptosis in osteosarcoma cells, which indicated that POR plays an important role in ferroptosis. Moreover, we also found that ZOL inhibits osteosarcoma growth in vivo. Our findings suggest that ZOL induces ferroptosis by upregulating POR expression to increase ROS levels and upregulate lipid peroxidation levels in osteosarcoma cells. POR may be used as a therapeutic target to inhibit osteosarcoma.
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