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Nitidine Chloride inhibits breast cancer cells migration and invasion by suppressing c-Src/FAK associated signaling
Xinhua Pan1, Honghui Han, Lei Wang
1The Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, 500 Dongchuan Road, Shanghai 200241, China.
Abstract:
Nitidine is a benzophenanthridine alkaloid, which has been shown to have anti-tumor properties. Here, we demonstrated that Nitidine Chloride (NC) could inhibit breast cancer cells migration and invasion both in vitro and in vivo. Meanwhile, the protrusion formation and partial proteolytic activity of MMP-9 and MMP-2 were attenuated by NC in a dose-dependent manner in MDA-MB-231 cells. Furthermore, addition NC to cells significantly decreases PDGF induced phosphorylation of c-Src, FAK, MAPKs, activation of RhoA, Rac1 and AP-1 transcriptional activity. Taken together, our results indicate that NC could have potential as a novel anti-metastasis drug to breast cancer.
Insights
Nitidine Chloride (NC) effectively inhibits breast cancer cell migration and invasion. This novel compound shows potential as an anti-metastasis drug by targeting key cellular pathways involved in cancer spread.
Area of Science:
- Pharmacology
- Oncology
- Molecular Biology
Background:
- Nitidine is a benzophenanthridine alkaloid with known anti-tumor properties.
- Cancer metastasis remains a significant challenge in breast cancer treatment.
Purpose of the Study:
- To investigate the anti-metastatic effects of Nitidine Chloride (NC) on breast cancer cells.
- To elucidate the molecular mechanisms underlying NC's action.
Main Methods:
- In vitro and in vivo studies using breast cancer cell lines (MDA-MB-231).
- Assays for cell migration, invasion, and matrix metalloproteinase (MMP) activity.
- Western blotting to assess protein phosphorylation and activation of signaling pathways (c-Src, FAK, MAPKs, RhoA, Rac1, AP-1).
Main Results:
- NC significantly inhibited breast cancer cell migration and invasion.
- NC dose-dependently attenuated protrusion formation and MMP-2/MMP-9 activity.
- NC decreased PDGF-induced phosphorylation of c-Src, FAK, MAPKs, and inhibited RhoA, Rac1 activation and AP-1 transcriptional activity.
Conclusions:
- Nitidine Chloride demonstrates potent anti-metastatic properties in breast cancer.
- NC acts by inhibiting key signaling pathways crucial for cancer cell motility and invasion.
- NC holds promise as a novel therapeutic agent for preventing breast cancer metastasis.
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