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Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway

YIWEN ZHU1, LIU YANG1, YING YU1, YING XIONG2, PING XIAO2, XIAO FU2, XIN LUO2,*

1 Department of Rehabilitation Medicine, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China
2 Department of General Practice, The Second Affiliated Hospital of Nanchang University, Nanchang, 330006, China

* Corresponding Author: XIN LUO. Email: email

(This article belongs to the Special Issue: Signaling Pathway Crosstalk in Malignant Tumors: Molecular Targets and Combinatorial Therapeutics)

Oncology Research 2024, 32(5), 899-910. https://doi.org/10.32604/or.2023.042604

Abstract

Osteosarcoma is a very serious primary bone cancer with a high death rate and a dismal prognosis. Since there is no permanent therapy for this condition, it is necessary to develop a cure. Therefore, this investigation was carried out to assess the impacts and biological functions of hydroxysafflor yellow A (HYSA) in osteosarcoma cell lines (MG63). In this investigational study, MG63 cells were utilized. Microarray experiments, quantitative polymerase chain reaction (qPCR), immunofluorescent staining, extracellular acidification rate (ECAR), oxygen consumption rate (OCR), glucose consumption, lactate production, and ATP levels, proliferation assay, 5-Ethynyl-2′-deoxyuridine (EDU) staining, and Western blot were performed. In MG63 cells, HYSA lowered cell proliferation and metastasis rates, suppressed EDU cell number, and enhanced caspase-3/9 activity levels. HYSA reduced the Warburg effect and induced ferroptosis (FPT) in MG63 cells. Inhibiting ferroptosis diminished HYSA’s anti-cancer activities in MG63 cells. The stimulation of the HIF-1α/SLC7A11 pathway decreased HYSA’s anti-cancer activities in MG63 cells. HIF-1α is one target spot for HYSA in a model of osteosarcoma cancer (OC). HYSA altered HIF-1α’s thermophoretic activity; following binding with HYSA, HIF-1α’s melting point increased from ~55°C to ~60°C. HYSA significantly enhanced the thermal stability of exogenous WT HIF-1α while not affecting Mut HIF-1α, suggesting that ARG-311, GLY-312, GLN-347, and GLN-387 may be involved in the interaction between HIF-1α and HYSA. Conclusively, our study revealed that HYSA induced FPT and reduced the Warburg effect of OC through mitochondrial damage by HIF-1α/HK2/SLC7A11 pathway. HYSA is a possible therapeutic option for OC or other cancers.

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APA Style
ZHU, Y., YANG, L., YU, Y., XIONG, Y., XIAO, P. et al. (2024). Hydroxysafflor yellow A induced ferroptosis of osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway. Oncology Research, 32(5), 899-910. https://doi.org/10.32604/or.2023.042604
Vancouver Style
ZHU Y, YANG L, YU Y, XIONG Y, XIAO P, FU X, et al. Hydroxysafflor yellow A induced ferroptosis of osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway. Oncol Res. 2024;32(5):899-910 https://doi.org/10.32604/or.2023.042604
IEEE Style
Y. ZHU et al., "Hydroxysafflor yellow A induced ferroptosis of Osteosarcoma cancer cells by HIF-1α/HK2 and SLC7A11 pathway," Oncol. Res., vol. 32, no. 5, pp. 899-910. 2024. https://doi.org/10.32604/or.2023.042604



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