Tranilast inhibits the cell growth of normal human keratinocytes in vitro.
Tranilast is used clinically as a drug for hypertrophic scars or keloids. Recently, the roles of keratinocytes in the pathogenesis of those conditions have been noted. Therefore, we first examined the effect of tranilast on the cell growth of normal human keratinocytes. A cell growth assay demonstrated that the cell number significantly decreased during 48 h cultures with the addition of tranilast (5-400 μM) compared with a control (tranilast 0) in a dose-dependent manner. Morphologically, cell spreading was decreased and the cell body was elongated with higher concentrations (200-400 μM) of tranilast, and the cell area decreased significantly. The effect was not due to cytotoxicity. The inhibition of cell growth and the changes in cell morphology by the treatment of 100 μM tranilast reversed after the removal of the tranilast. Immunohistochemical staining revealed that F-actin and vinculin expression with tranilast-treated keratinocytes decreased significantly in a dose-dependent manner (100-400 μM). In addition, cell cycle examination showed that 400 μM of tranilast caused G0/G1 arrest with the keratinocytes. From these data we concluded that tranilast inhibited the growth of normal human keratinocytes, and one of its mechanisms may involve decreasing cell spreading by inhibition of F-actin fiber and focal contact formation with the cells.
Department of Plastic and Reconstructive Surgery, Kawasaki Medical School, Kurashiki, Okayama, Japan. mkubo@cc.okayama-u.ac.jp
Miyoko
M
Kubo
Ying
Y
Zhao
Takahiko
T
Moriguchi
D000199:Actins / Q000378:metabolism; D018926:Anti-Allergic Agents / Q000494:pharmacology*; D002452:Cell Count; D002453:Cell Cycle / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects*; D002478:Cells, Cultured; D004305:Dose-Response Relationship, Drug; D006801:Humans; D066298:In Vitro Techniques; D015603:Keratinocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism; D013997:Time Factors; D016596:Vinculin / Q000378:metabolism; D062367:ortho-Aminobenzoates / Q000494:pharmacology*
D000199:Actins; D018926:Anti-Allergic Agents; D062367:ortho-Aminobenzoates; D016596:Vinculin; C012293:tranilast