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Investigation of inhibition effect of daidzein on osteosarcoma cells based on experimental validation and systematic
Yufan Zhu1, Zhiqiang Yang1, Yuanlong Xie1
1Department of Spine Surgery & Musculoskeletal Tumor, Zhongnan Hospital of Wuhan University, Wuhan, Hubei, People's Republic of China.
Objective:
This study aims to explore the effect of daidzein, which is a natural isoflavone compound mainly extracted from soybeans, on osteosarcoma and the potential molecular mechanism.
Material And Methods:
143B and U2OS osteosarcoma cells were treated with gradient concentrations of daidzein, and MTT assay was used to determine the cell proliferation capacity and IC50. Hoechst 33342 staining and Annexin V-FITC/PI detection were used to determine apoptosis. Cell cycle was analyzed by flow cytometry, and migration ability were detected by transwell assays and scratch wound assay. An osteosarcoma xenograft mice model was applied to investigate the effect of daidzein on osteosarcoma in vivo. Systematic pharmacology and molecular modeling analysis were applied to predict the target of daidzein to osteosarcoma, and the target Src was verified by western blotting. We also observed the effect of daidzein on cell proliferation and apoptosis of Src-overexpressing osteosarcoma cells.
Results:
In vitro, daidzein significantly inhibited 143B and U2OS osteosarcoma cell proliferation and migration, and induced cell cycle arrest. In vivo, daidzein exerts antitumor effects in osteosarcoma xenograft mice. After systematic screening and analysis, Src-MAPK signaling pathway was predicted as the highest-ranked pathway. Western blot demonstrated that daidzein inhibited phosphorylation of the Src-ERK pathway in osteosarcoma cells. Also, overexpression of Src could partially reverse the inhibitory effects of daidzein on osteosarcoma cell proliferation.
Conclusion:
Daidzein exerts an antitumor effect on osteosarcoma, and the mechanism may be through the Src-ERK pathway.
Insights
Daidzein, a soy isoflavone, inhibits osteosarcoma cell growth and migration by targeting the Src-ERK pathway. This natural compound shows potential as an antitumor agent for osteosarcoma, both in vitro and in vivo.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Osteosarcoma is a primary bone malignancy with limited effective treatments.
- Daidzein, a soy-derived isoflavone, has shown potential anticancer properties.
- Understanding daidzein's molecular mechanisms in osteosarcoma is crucial for therapeutic development.
Purpose of the Study:
- To investigate the antitumor effects of daidzein on osteosarcoma cells.
- To elucidate the molecular mechanism underlying daidzein's action in osteosarcoma.
- To evaluate daidzein's efficacy in an osteosarcoma xenograft mouse model.
Main Methods:
- Cell proliferation, apoptosis, cell cycle, and migration assays were performed on osteosarcoma cell lines treated with daidzein.
- An in vivo osteosarcoma xenograft mouse model was used to assess daidzein's antitumor activity.
- Systematic pharmacology, molecular modeling, and Western blotting were employed to identify and verify daidzein's molecular targets, focusing on the Src-ERK pathway.
Main Results:
- Daidzein significantly inhibited osteosarcoma cell proliferation and migration in vitro.
- Daidzein induced cell cycle arrest and apoptosis in osteosarcoma cells.
- In vivo studies confirmed daidzein's antitumor effects in a mouse model, with evidence suggesting the Src-ERK pathway is involved.
- Overexpression of Src partially reversed daidzein's inhibitory effects, confirming Src's role.
Conclusions:
- Daidzein demonstrates significant antitumor activity against osteosarcoma.
- The mechanism of action involves the inhibition of the Src-ERK signaling pathway.
- Daidzein represents a promising natural compound for osteosarcoma therapy.
