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Updated: May 9, 2026
Analysis of Cell Migration within a Three-dimensional Collagen Matrix
Published on: October 5, 2014
Inhibition of Src activation with cardiotoxin III blocks migration and invasion of MDA-MB-231 cells
Pei-Chien Tsai1, Chiao-Lun Chu, Chien-Chih Chiu
1Department of Medicinal and Applied Chemistry, Kaohsiung Medical University, Kaohsiung 807, Taiwan.
Abstract:
Cardiotoxin III (CTX III), a basic polypeptide isolated from Naja naja atra venom, has been demonstrated to display anticancer activity. Breast cancer is a highly malignant carcinoma and most deaths of breast cancer are caused by metastasis. In this study, we show that CTX III blocks migration and invasion of MDA-MB-231 breast cancer cells without affecting apoptosis or cell cycle arrest. CTX III caused significant block of Src kinase activity in MDA-MB-231 cells. Moreover, CTX III treatment was correlated with reduced phosphorylation of FAK at Tyr576, 861 and 925 sites, p130(Cas) at Tyr410, and paxillin at Tyr118. CTX III also suppressed the activation of extracellular signal-regulated kinase1/2 and phosphatidylinositol 3-kinase/Akt. Consistent with inhibition of these signaling pathways and invasion, CTX III inhibited the expression of matrix metalloproteinase-9. In addition, Src specific inhibitor PP2 caused a significant decrease in the phosphorylation of FAK, p130(Cas), paxillin, PI3K/Akt, and ERK1/2. Taken together, CTX III significantly inhibited phosphorylation of Src and downstream molecules as well as cell migration and invasion. Our findings provide evidences that CTX III inhibits Src-mediated signaling pathways involved in controlling MDA-MB-231 cell migration and invasion, suggesting that it has therapeutic potential in breast cancer treatment.
Insights
Cardiotoxin III (CTX III) from cobra venom inhibits breast cancer cell migration and invasion by blocking the Src signaling pathway. This suggests CTX III has therapeutic potential for treating metastatic breast cancer.
Area of Science:
- Biochemistry
- Molecular Biology
- Cancer Research
Background:
- Breast cancer metastasis is a primary cause of mortality.
- Cardiotoxin III (CTX III), a polypeptide from Naja naja atra venom, exhibits anticancer properties.
Purpose of the Study:
- To investigate the effect of CTX III on the migration and invasion of MDA-MB-231 breast cancer cells.
- To elucidate the underlying molecular mechanisms, particularly the role of Src signaling.
Main Methods:
- Treatment of MDA-MB-231 cells with CTX III.
- Assessment of cell migration, invasion, apoptosis, and cell cycle.
- Western blot analysis to measure protein phosphorylation and activation of signaling pathways (Src, FAK, p130(Cas), paxillin, ERK1/2, PI3K/Akt).
- Inhibition of matrix metalloproteinase-9 (MMP-9) expression.
Main Results:
- CTX III significantly blocked MDA-MB-231 cell migration and invasion without affecting apoptosis or cell cycle.
- CTX III inhibited Src kinase activity and the phosphorylation of downstream molecules including FAK, p130(Cas), and paxillin.
- Activation of ERK1/2 and PI3K/Akt pathways was suppressed by CTX III.
- Expression of MMP-9 was reduced following CTX III treatment.
Conclusions:
- CTX III effectively inhibits breast cancer cell migration and invasion by targeting Src-mediated signaling pathways.
- CTX III demonstrates therapeutic potential for treating metastatic breast cancer.
