Strobilanthes crispus inhibits migration, invasion and metastasis in breast cancer

Ethnopharmacological relevance: Strobilanthes crispus (L.) Blume, locally known in Malaysia as Pecah kaca or Jin batu, has been traditionally used for treatment of various ailments including cancer. We previously demonstrated that a standardized bioactive subfraction of S. crispus, termed as F3, possessed potent anticancer effects in both in vitro and in vivo breast cancer models. Aim of the study: To investigate the potential of F3 from S. crispus to prevent metastasis in breast cancer. Materials and methods: The antimetastatic effects of F3 were first investigated on murine 4T1 and human MDA-MB-231 breast cancer cell (BCC) lines using cell proliferation, wound healing and invasion assays. A 4T1-induced mouse mammary carcinoma model was then used to determine the expression of metastasis tumor markers, epithelial (E)-cadherin, matrix metalloproteinase (MMP)-9, mucin (MUC)-1, nonepithelial (N)-cadherin, Twist, vascular endothelial growth factor (VEGF) and vimentin, using immunohistochemistry, following oral treatment with F3 for 30 days. Results: Significant growth arrest was observed with F3 IC50 values of 84.27 mu g/ml (24 h) and 74.41 mu g/ml (48 h) for MDA-MB-231, and 87.35 mu g/ml (24 h) and 78.75 mu g/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 mu g/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 mu g/ml, p = 0.016) and MDA-MB-231 (50 mu g/ml, p = 0.040) cells compared to the untreated cultures. F3 treatment resulted in reduced tumor growth compared to untreated mice (p < 0.01) or mice treated with tamoxifen (p < 0.05). Statistical parameters (absolute count, proportion, intensity and overall scores) indicating upregulation of E-cadherin expression were statistically significant in F3 treated compared to the untreated tumor-bearing mice. Similarly, F3 significantly reduced the expression of MMP-9, MUCI, N-cadherin, Twist, VEGF and vimentin in comparison with the TM (p < 0.01) group Conclusions: Our findings suggest that F3 exerts anti-metastatic effects independent of its cytotoxic effects, and these are supported by the increased expression of E-cadherin concurrent with downregulation of MMP-9, MUCI, N-cadherin, Twist, VEGF and vimentin expression in breast cancer.