The antitumour activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole in human gastric cancer models is mediated by AhR signalling.

ABSTRACT: Stomach cancer is the fourth most common cancer worldwide. Identification of novel molecular therapeutic targets and development of novel treatments are critical. Against a panel of gastric carcinoma cell lines, the activity of 2-(4-amino-3-methylphenyl)-5-fluorobenzothiazole (5F 203) was investigated. Adopting RT-PCR, Western blot and immunohistochemical techniques, we sought to determine molecular pharmacodynamic (PD) markers of sensitivity and investigate arylhydrocarbon (AhR) receptor-mediated signal transduction activation by 5F 203. Potent (IC₅₀  ≤ 0.09 μmol/L), selective (>250-fold) in vitro antitumour activity was observed in MKN-45 and AGS carcinoma cells. Exposure of MKN-45 cells to 5F 203 triggered cytosolic AhR translocation to nuclei, inducing CYP1A1 (>50-fold) and

SUBMITTER: Wang Y 

PROVIDER: S-EPMC6991636 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature