Diosmetin inhibits cell proliferation and promotes apoptosis through STAT3/c-Myc signaling pathway in human osteosarcoma cells

Biological Research

Guang Chen¹  Rende Ning¹  Run Fang¹  Yanhui Zhang²  Wenjuan Zhao³  Feng Qian³ 

[1] Department of Orthopaedics, The Third Affiliated Hospital of Anhui Medical University, 390 Huaihe Road, 230031, Hefei, China;Department of Otolaryngology Head and Neck Surgery, Shanghai General Hospital, 85 Wu Jin Road, 200080, Shanghai, China;Engineering Research Center of Cell & Therapeutic Antibody, Ministry of Education, School of Pharmacy, Shanghai Jiao Tong University, 800 Dongchuan Road, 200240, Shanghai, China;

关键词: Diosmetin;    Osteosarcoma;    Signal transducer and activator of transcription 3 (STAT3);    Cell proliferation;    Apoptosis;   

DOI  :  10.1186/s40659-021-00363-1

来源: Springer

【 摘 要 】

BackgroundDiosmetin is a bioflavonoid compound naturally abundant in citrus fruits. It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown.MethodsColony formation assay, cell cycle analysis and apoptosis analysis were conducted respectively to observe the effect of diosmetin on cell proliferation and apoptosis in human osteosarcoma cells. Western blot and immunoprecipitation were used to detect the expression of apoptotic molecules and activation of STAT3/c-Myc pathway in Saos-2 and U2SO cells.ResultsDiosmetin significantly inhibited cell proliferation, induced cell cycle arrest at G2/M phase and promoted cell apoptosis in both Saos-2 and U2SO cells. Moreover, Diosmetin downregulated the expression of anti-apoptotic protein Bcl-xL while upregulated the levels of pro-apoptotic proteins including cleaved Caspase-3, cleaved-PARP and Bax. Furthermore, diosmetin dose-dependently inhibited STAT3 phosphorylation, reduced the expression of its downstream protein c-Myc and impeded the interaction between STAT3 molecules.ConclusionsThese results suggest that diosmetin exerts anti-osteosarcoma effects by suppressing cell proliferation and inducing apoptosis via inhibiting the activation of STAT3/c-Myc signaling pathway, which provide the possibility for diosmetin to be a chemotherapeutic candidate for osteosarcoma.

【 授权许可】

CC BY