Inhibition of growth and metastasis of breast carcinoma by tranilast

1176 Tranilast (N-[3, 4 - dimethoxycin-namoyl]-anthranalic acid) is used clinically in Japan as an anti-allergic agent and to control fibrotic disorders. The anti-fibrotic effect of tranilast is thought to be mediated through the inhibition of TGF-β1 and possibly other mediators. Tranilast has also been shown to inhibit the growth of many tumor cells, such as glioma cells, uterine leiomyoma cells, oral squamous cell carcinoma and pancreatic tumor. It is well tolerated and has few adverse effects as compared to conventional anticancer drugs. In the present study, we explored the anti-tumor effect of tranilast in experimental mammary tumor, as the metastasis of breast cancer very much depends on TGF-β1. BALB/c mice were inoculated with syngenic mammary tumor cells (4T1) in mammary fat pads and tranilast was given daily by gavage. Tumor volumes were measured at various time points. After 4 weeks, mice were sacrificed and various tissues were fixed for routine histology. Our results showed that tranilast markedly reduced (> 50 %) the growth of the primary tumor in vivo. The drug also drastically reduced (> 90 %) metastases to the lungs and liver. In addition, tranilast suppressed the growth of 4T1 cells in a dose-dependent manner in culture, without any cytotoxic effect. Growth of human MDA-MB-231 breast tumor cells and other cancer cells were also inhibited by tranilast in culture. Tranilast inhibited the epithelial to mesenchymal transdifferentiation of 4T1, which is important for metastasis. Thus, these results showed that the tranilast has potential to be an effective therapeutic agent in breast cancer.