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 µg/ml (24 h) and 74.41 µg/ml (48 h) for MDA-MB-231, and 87.35 µg/ml (24 h) and 78.75 µg/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 μg/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 µg/ml, p = 0.016) and MDA-MB-231 (50 µg/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, MUC1, 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, MUC1, N-cadherin, Twist, VEGF and vimentin expression in breast cancer.
["Baraya|Yusha'u Shu'aibu|YS|", 'Wong|Kah Keng|KK|', 'Yaacob|Nik Soriani|NS|']
D027901:Acanthaceae D000818:Animals D000970:Antineoplastic Agents D001943:Breast Neoplasms D015820:Cadherins D045744:Cell Line, Tumor D002465:Cell Movement D049109:Cell Proliferation D005260:Female D006801:Humans D020780:Matrix Metalloproteinase 9 D008807:Mice, Inbred BALB C D018396:Mucin-1 D008517:Phytotherapy D010936:Plant Extracts D018515:Plant Leaves D051879:Twist-Related Protein 1 D042461:Vascular Endothelial Growth Factor A D014945:Wound Healing
Strobilanthes crispus 4T1 MDA-MB-231 Anti-invasion Antimetastasis Antimigration