ReferenceID 5606
Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin-DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
Int J Mol Sci
Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora
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Record Fields
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- Reference Id
- 5606
- Evidence Id
- 22196
- Core Evidence Id
- 22196
- Source Reference Id
- 4426
- Herb2 Reference Id
- HBREF005223
- Subject Paper Key
- HBIN033231_35163790
- Pubmed Id
- 35163790
- Doi
- 10.3390/ijms23031868
- Paper Title
- Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin-DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
- Paper Abstract
- Aurora A kinase (Aurora A) is a serine/threonine kinase regulating control of multiple events during cell-cycle progression. Playing roles in promoting proliferation and inhibiting cell death in cancer cells leads Aurora A to become a target for cancer therapy. It is overexpressed and associated with a poor prognosis in ovarian cancer. Improving cisplatin therapy outcomes remains an important issue for advanced-stage ovarian cancer treatment, and Aurora A inhibitors may improve it. In the present study, we identified natural compounds with higher docking scores than the known Aurora A ligand through structure-based virtual screening, including the natural compound fangchinoline, which has been associated with anticancer activities but not yet investigated in ovarian cancer. The binding and inhibition of Aurora A by fangchinoline were verified using cellular thermal shift and enzyme activity assays. Fangchinoline reduced viability and proliferation in ovarian cancer cell lines. Combination fangchinoline and cisplatin treatment enhanced cisplatin-DNA adduct levels, and the combination index revealed synergistic effects on cell viability. An in vivo study showed that fangchinoline significantly enhanced cisplatin therapeutic effects in OVCAR-3 ovarian cancer-bearing mice. Fangchinoline may inhibit tumor growth and enhance cisplatin therapy in ovarian cancer. This study reveals a novel Aurora A inhibitor, fangchinoline, as a potentially viable adjuvant for ovarian cancer therapy.
- Journal
- Int J Mol Sci
- Publish Year
- 2022
- Experiment Subject
- mouse; ovarian cancer cell lines
- Experiment Type
- Animal & Cell Experiment
- Phenotype Related
- Ovcar-3 Ovarian Cancer; Ovarian Cancer; Tumor; Advanced-stage Ovarian Cancer; Cancer
- Paper Title Cn
- Paper Title En
- Novel Aurora A Kinase Inhibitor Fangchinoline Enhances Cisplatin-DNA Adducts and Cisplatin Therapeutic Efficacy in OVCAR-3 Ovarian Cancer Cells-Derived Xenograft Model
- Bilingual Status
- semi_complete