Oxidative stress induction by narasin augments doxorubicin’s efficacy in osteosarcoma

BMC Pharmacology and Toxicology

Research

Feng Bian¹  Ping Wang¹  Zhaoming Han²  Juguang Yang²  Jiguang Jia² 

[1] Department of Orthopedics, Wuhan Third Hospital, Tongren Hospital of Wuhan University, Pengliuyang Road 241, Wuchang District, 430064, Wuhan, China;Department of Orthopedics, Xiangyang No. 1 People’s Hospital, Hubei University of Medicine, 15 Jiefang Road, Fancheng District, Xiangyang, 441000, China;

关键词: Narasin;    Doxorubicin;    Synergism;    Oxidative stress;    Osteosarcoma;   

DOI  :  10.1186/s40360-023-00695-6

 received in 2023-02-02, accepted in 2023-10-09,  发布年份 2023

来源: Springer

【 摘 要 】

Complications and fata toxicity induced by chemotherapy are the main challenge for clinical management of osteosarcoma. The identification of agents that can augment the efficacy of chemotherapy at lower doses may represent an alternative therapeutic strategy. Narasin is a polyether antibiotic widely used in veterinary medicine. In this study, we show that narasin is active against osteosarcoma cells at the same concentrations that are less toxic to normal cells. This effect is achieved by growth inhibition and apoptosis induction, which is mediated by oxidative stress and damage, and mitochondrial dysfunction. The antioxidant N-acetyl-l-cysteine (NAC) abolishes the anti-osteosarcoma activity. Importantly, narasin significantly augments doxorubicin’s efficacy in both osteosarcoma cell culturing system and subcutaneous implantation mouse model. The combination of narasin and doxorubicin at non-toxic doses completely arrests osteosarcoma growth in mice. Our results suggest that the concurrent administration of doxorubicin and narasin could present a viable alternative therapeutic approach for osteosarcoma.

【 授权许可】

CC BY   
© BioMed Central Ltd., part of Springer Nature 2023

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