Tranilast treatment decreases cell growth, migration and inhibits colony formation of human breast cancer cells.
In the treatment of breast cancer, although a wide of choice of drugs and treatment modalities are available, drug resistance or drug toxicity poses a considerable challenge. Tranilast is a well tolerated drug used in the treatment of allergic disorders. Previous works in various models have shown that tranilast has the potential to be used as an anti-cancer drug. Hence, in this study using human breast cancer cell lines BT-474 and MDA-MB-231, we studied the effect of tranilast on cell growth, migration and ability to prevent colony formation in vitro, properties that are relevant to a possible therapeutic effect in breast cancer. We found that tranilast inhibits the growth of both breast cancer cell lines. In the cell migration experiments, the tumor cells exhibit significantly slower wound closure after tranilast treatment, as well as reduced migration using an insert system. Downregulation of MRTF-A, a global cytoskeleton regulator was observed after tranilast treatment. Additionally, tranilast treatment increased levels of cleaved PARP in both cell lines tested indicating a stimulation of apoptosis. A significant reduction in colony size and number was observed in soft agar clonogenic assays in both cell lines after tranilast treatment. BT-474 cells were more responsive to tranilast treatment compared to MDA-MB-231 cells, suggesting a difference in modes of action, or sensitivity, possibly related to their different receptor status. Based on these changes in cancer cell lines, we conclude that tranilast exerts effects that set a rationale for future preclinical studies in animal models of breast cancer.
Department of Laboratory Medicine and Keenan Research Centre of the Li Ka Shing Knowledge Institute, St Michael's Hospital, Toronto, Ontario, Canada.
Venkateswaran
V
Subramaniam
Olga
O
Ace
Gerald J
GJ
Prud'homme
Serge
S
Jothy
D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects*; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D003114:Colony-Forming Units Assay; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D011065:Poly(ADP-ribose) Polymerases / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology / Q000627:therapeutic use*
D000970:Antineoplastic Agents; D062367:ortho-Aminobenzoates; D011065:Poly(ADP-ribose) Polymerases; C012293:tranilast