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Network Pharmacology Integrated Molecular Docking Reveals the Antiosteosarcoma Mechanism of Biochanin A
Qing Luo1, Xuan Shi2, Jiarong Ding3
1Department of Oncology Laboratory, Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Background:
As the malignant tumor with the highest incidence in teenagers, osteosarcoma has become a major problem in oncology research. In addition to surgical management, the pharmacotherapeutic strategy for osteosarcoma treatment is an attractive way to explore. It has been demonstrated that biochanin A has an antitumor capacity on multiple kinds of solid tumor, including osteosarcoma. But the precise mechanism of biochanin A against osteosarcoma is still needed to be discovered.
Objective:
To identify the potential therapeutic targets of biochanin A in treating osteosarcoma.
Methods:
In present study, an integrated approach including network pharmacology and molecular docking technique was conducted, which mainly comprises target prediction, network construction, gene ontology, and pathway enrichment. CCK8 test was employed to evaluate the cell viability of MG63 cells. Western-blot was used to verify the target proteins of biochanin A.
Results:
Ninety-six and 114 proteins were obtained as the targets of biochanin A and osteosarcoma, respectively. TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF were identified as the potential targets of biochanin A against osteosarcoma. Based on the western-blot detection, the expression of BGLAP, BAX, and ATF3 in MG63 cell line changed under the treatment of biochanin A.
Conclusion:
Biochanin A can effectively suppress the proliferation of osteosarcoma and regulate the expression of BGLAP, BAX, and ATF3, which may act as the potential therapeutic targets of osteosarcoma.
Insights
Biochanin A shows potential in treating osteosarcoma by suppressing tumor cell proliferation. This study identified key targets like BGLAP, BAX, and ATF3, offering new avenues for osteosarcoma pharmacotherapy.
Area of Science:
- Oncology
- Pharmacology
- Molecular Biology
Background:
- Osteosarcoma is a prevalent cancer in teenagers, necessitating novel therapeutic strategies beyond surgery.
- Biochanin A exhibits antitumor properties against various solid tumors, including osteosarcoma.
- The precise mechanism of biochanin A's action in osteosarcoma requires further elucidation.
Purpose of the Study:
- To identify potential therapeutic targets of biochanin A for osteosarcoma treatment.
- To elucidate the molecular mechanisms underlying biochanin A's efficacy against osteosarcoma.
Main Methods:
- Integrated network pharmacology and molecular docking for target prediction and network construction.
- Gene Ontology (GO) and pathway enrichment analyses to understand functional implications.
- Cell viability assays (CCK8) and Western blotting to validate target protein expression.
Main Results:
- Identified 96 and 114 protein targets for biochanin A and osteosarcoma, respectively.
- Highlighted TP53, IGF1, JUN, BGLAP, ATM, MAPK1, ATF3, H2AFX, BAX, CDKN2A, and EGF as key potential targets.
- Confirmed changes in BGLAP, BAX, and ATF3 expression in MG63 cells treated with biochanin A.
Conclusions:
- Biochanin A effectively suppresses osteosarcoma cell proliferation.
- BGLAP, BAX, and ATF3 are identified as key regulatory targets of biochanin A in osteosarcoma.
- These findings suggest biochanin A as a promising therapeutic agent for osteosarcoma.
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