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Updated: Jun 10, 2026

Studying TGF-β Signaling and TGF-β-induced Epithelial-to-mesenchymal Transition in Breast Cancer and Normal Cells
Published on: October 27, 2020
Cryptotanshinone Directly Targets MEK1 to Inhibit Migration and Invasion of Breast Cancer Cells Through
Min Qian1, Xin Liu1, Zhuoran Chai1
1School of Chemistry and Life Science, Suzhou University of Science and Technology, Suzhou, China.
Abstract:
Cryptotanshinone (CPT) exerts inhibitory effects on breast cancers (BC). However, its effect and potential mechanism on breast cancer cell migration and invasion are not well understood. This study aims to investigate the potential mechanism of CPT on migration and invasion by network pharmacology and experiments. Wound healing and Transwell Matrigel invasion assays were performed to analyze the effects of CPT on migration and invasion in breast cancer cell lines MCF-7 and 4 T1. Western blot and immunofluorescence analyses were performed to verify the effect of CPT on epithelial-mesenchymal transition (EMT). Network pharmacology and experiments were used to explore the potential mechanism of CPT on EMT in breast cancer. Molecular docking, molecular dynamics (MD) simulation, cellular thermal shift assays (CETSA), drug affinity responsive target stability (DARTS), transfection, and mutagenesis were performed to confirm the direct binding effect of CPT on MEK1. Finally, BC nude mouse xenografts were established to explore the anti-metastasis effect of CPT in vivo. We found that CPT inhibited the EMT process to attenuate the migration and invasion of BC cells in a dose-dependent manner. Subsequently, network pharmacology, CETSA, DARTS, and enzyme activity assays confirmed that CPT directly binds MEK1 to inhibit its phosphorylation and kinase activity. Moreover, the molecular docking, MD, and mutagenesis results showed that CPT bound to MEK1 at Gly80 and Asp208. Moreover, MEK inhibitor (AZD-6244) intervention studies confirmed that CPT inhibits EMT by targeting the MEK pathway. Finally, the mouse tail vein injection model showed that CPT can effectively inhibit BC metastasis in vivo. Our results demonstrated that CPT modulates breast cancer migration and invasion via the MEK/ERK/EMT axis by directly targeting MEK1. Our study provides evidence suggesting that CPT may serve as a potential agent for suppressing breast cancer metastasis.
Insights
Cryptotanshinone (CPT) inhibits breast cancer cell migration and invasion by targeting MEK1, suppressing the MEK/ERK/EMT pathway. This study reveals CPT
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Cryptotanshinone (CPT) shows inhibitory effects on breast cancer (BC).
- The precise mechanisms by which CPT affects breast cancer cell migration and invasion remain unclear.
- Understanding CPT's mechanism is crucial for developing novel anti-metastasis therapies.
Purpose of the Study:
- To investigate the mechanism of CPT on breast cancer cell migration and invasion.
- To explore the role of CPT in epithelial-mesenchymal transition (EMT).
- To validate CPT's direct binding to MEK1 and its anti-metastasis effects in vivo.
Main Methods:
- Network pharmacology, wound healing, and Transwell assays were used to analyze CPT's effects on BC cell migration and invasion.
- Western blot, immunofluorescence, molecular docking, MD simulations, CETSA, and DARTS were employed to elucidate the mechanism.
- In vivo studies using BC nude mouse xenografts and tail vein injection models assessed anti-metastasis efficacy.
Main Results:
- CPT dose-dependently inhibited EMT, reducing breast cancer cell migration and invasion.
- CPT directly binds to MEK1, inhibiting its phosphorylation and kinase activity.
- CPT suppressed breast cancer metastasis in vivo, targeting the MEK/ERK/EMT axis.
Conclusions:
- CPT suppresses breast cancer metastasis by targeting MEK1 and inhibiting the MEK/ERK/EMT pathway.
- CPT demonstrates potential as an anti-metastasis agent for breast cancer treatment.
- This study provides mechanistic insights into CPT's anti-cancer properties.
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