Abstract
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.
Highlights
Diosmetin is a bioflavonoid compound naturally abundant in citrus fruits
Diosmetin inhibited the proliferation of osteosarcoma cells In order to identify the anti-tumor activity of diosmetin, 3′,5,7-trihydroxy-4′-methoxyflavone (Fig. 1A), in osteosarcoma cells, we investigated its anti-proliferative role using colony formation assay on human osteosarcoma Saos-2 and U2SO cell lines
Quantification analysis of the colony numbers of both Saos-2 and U2SO cells revealed that diosmetin hindered cell proliferation of osteosarcoma cells in a dose-dependent manner (Fig. 1C and D) and diosmetin at 0.9 μM for 10 days almost completely inhibited cell proliferation of both Saos-2 and U2SO cells (Fig. 1B, C, and D), representing a strong inhibitory effect of diosmetin on osteosarcoma cells
Summary
It is found to perform a variety of activities, while its antitumor property in osteosarcoma, a malignant tumor with unmet clinical treatment, remained unknown. Ning et al Biological Research (2021) 54:40 from cytoplasm into the nucleus, triggering the transcription of the downstream genes involved in tumor proliferation and survival [4]. It has been demonstrated STAT3 plays a vital role in osteosarcoma development and might be a promising target for drug discovery of human osteosarcoma [5,6,7]. A variety of natural products with STAT3 inhibitory activity such as curcumin, resveratrol and JSI-124 (cucurbitacin I), have been isolated from natural products, and most are branched and flavonoids [9,10,11,12]
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