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Nifuratel Induces Triple-Negative Breast Cancer Cell G2/M Phase Block and Apoptosis by Regulating GADD45A
Yuhang Hou1, Hongyun Hao1, Yan Yuan1
1New Drug Screening and Pharmacodynamics Evaluation Center, National Key Laboratory for Multi-Target Natural Drugs, China Pharmaceutical University, Nanjing 210000, China.
Pharmaceuticals (Basel, Switzerland)
|October 26, 2024
Summary
Nifuratel (NF113) demonstrates anti-tumor effects against triple-negative breast cancer by inhibiting proliferation and inducing apoptosis. This occurs through the upregulation of GADD45A, impacting key cell cycle and signaling pathways.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Nifuratel (NF113), a nitrofuran derivative, exhibits anti-tumor properties.
- The precise mechanisms of NF113 in triple-negative breast cancer (TNBC) are not fully understood.
- TNBC remains a challenging subtype with limited targeted therapies.
Purpose of the Study:
- To investigate the anti-tumor mechanisms of Nifuratel (NF113) in triple-negative breast cancer.
- To evaluate the efficacy of NF113 in both in vitro and in vivo models of TNBC.
- To elucidate the molecular pathways targeted by NF113 in breast cancer.
Main Methods:
- Cell proliferation was assessed using CCK8 and colony formation assays.
- Apoptosis and cell cycle distribution were analyzed via flow cytometry.
- Transcriptome sequencing, PCR, Western blot, and xenograft/organoid models were employed to validate mechanisms.
Main Results:
- NF113 demonstrated significant anti-tumor activity against TNBC in vitro and in vivo.
- NF113 treatment led to increased apoptosis and G2/M phase arrest in TNBC cells.
- NF113 reduced GADD45A expression, affecting downstream CDC25C and AKT phosphorylation.
Conclusions:
- Nifuratel (NF113) inhibits triple-negative breast cancer growth by upregulating GADD45A.
- NF113 may induce G2/M phase arrest via the GADD45A/CyclinB/CDK1 pathway.
- NF113-induced apoptosis may occur through the GADD45A/JNK/P38 pathway.
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