The effect of Tranilast, a TGFβ inhibitor on the colon cancer cell proliferation

Background and Aim: Colon cancer is the third most common malignant cancer and the second most common cause of cancer deaths around the world. So far, extensive research has been done on the causes and patterns of colon cancer formation and development, as well as on prevention and treatment. Tranilast is a TGFβ inhibitor and identified as an anti-allergic agent, and used in the treatment of inflammatory diseases, such as bronchial asthma, atypical dermatitis, allergic conjunctivitis, keloids and hypertrophic scars. The beneficial effects of Tranilast have also been seen in a variety of disease states, such as fibrosis, proliferative disorders, cardiovascular problems, autoimmune disorders, ocular diseases, diabetes and renal diseases. On the other hand, extensive research has been performed on its effects on various cancers. In this study, we evaluated the anti-cancer effects of this drug on colon cancer cell line.Methods: CT-۲۶ colon cancer cells were cultured in F۱۲ medium supplemented with ۱۰% FBS and antibiotic streptomycin and penicillin at ۳۷ ° C and ۵% CO۲. To evaluate the effect of Tranilast toxicity on cells, MTT assay and spheroid tests were used. The Real Time PCR technique was also used to examine the expression of cyclinD۱, VEGF, VEGFR and TGF-β genes at the RNA level. For evaluation the Cyclin-D۱protein expression western blotting was used.Results: The results revealed that the IC۵۰ of the Tranilast on CT-۲۶ cells was about ۲۰۰µM. Consistently, the spheroid test showed that after ۷ days, ۱mM of Tranilast disturbed spheroid structure and decreased spheroid volume, compared to the control group. The results of Real Time PCR showed that ۲۰۰ ?m dosage of Tranilast could decrease the expression of Cyclin D۱ gene and TGF-beta. Also the expression of VEGF-R was decreased.Conclusion: This study suggests that Tranilast anti-cancer properties by decreasing the expression of cell proliferation markers, Cyclin D۱ and TGF-β mRNA. These results support the therapeutic potency of Tranilast for colon cancer patients alone or with standard treatments.

Keywords:

Colon cancer , Tranilast , Real Time PCR , Cyclin-D۱