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Review
. 2021 Jul 12:30:100380.
doi: 10.1016/j.jbo.2021.100380. eCollection 2021 Oct.

Targeting ferroptosis in osteosarcoma

Jiazheng Zhao  1 , Yi Zhao  1 , Xiaowei Ma  1 , Benzheng Zhang  2 , Helin Feng  1
Affiliations
Review

Targeting ferroptosis in osteosarcoma

Jiazheng Zhao et al. J Bone Oncol. .

Abstract

Osteosarcoma (OS) is the most common primary bone tumour in children and adolescents, with high degree of malignancy and an extremely poor prognosis. Ferroptosis, a non-traditional mode of regulated cell death (RCD) characterised by iron-dependent accumulation of lipid reactive oxygen species (ROS), is closely associated with a variety of cancers. It has been demonstrated that ferroptosis can regulate OS progression and exert an essential role in the treatment of OS, which is potentially of great value. By targeting ferroptosis in OS, the present review article summarises the relevant mechanisms and therapeutic applications along with discussing current limitations and future directions, which may provide a new strategy for the treatment of OS.

Keywords: Ferroptosis; Iron; Osteosarcoma; Reactive oxygen species; Treatment.

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Conflict of interest statement

The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.

Figures

Fig. 1
Fig. 1
Occurrence and regulation of ferroptosis in osteosarcoma cells. The accumulation of ROS is necessary for the development of ferroptosis. The peroxidation of unsaturated fatty acids and the catalysis of iron are the initiating factors for the production of ROS, and the application of EF24 promotes the formation of ROS while Ferrostatin-1 and Liproxstatin-1 suppress this process. In addition, the GPX4 pathway, which is essential for the inhibition of ferroptosis by ROS scavenging, is regulated by several elements: Erastin and Sorafenib limit cystine transport by acting on System Xc‑; Tirapazamine suppresses SLC7A11; KDMA4 mediates the demethylation of SLC7A11 to promote cystine transit; PEITC down-values GSH level; Ferrate not only depletes GSH but also increases iron content; STAT3/Nrf2 pathway facilitates GPX4 production and RSL3 inhibits GPX4 generation. ROS, reactive oxygen species; EF24, 3,5-bis (2-fluorobenzylidine)-4- pyperidone; GPX4, glutathione peroxidase 4; KDM4A, lysine demethylase 4A; PEITC, β-phenethyl isothiocyanate; GSH, glutathione; STAT3, signal transducer and activator of transcription 3; Nrf2, nuclear factor erythroid 2-related factor 2.
See this image and copyright information in PMC

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