The 2-anilino-4-amino-5-aroylthiazole-type compound AS7128 inhibits lung cancer growth through decreased iASPP and p53 interaction

Abstract

Lung cancer is the leading cause of cancer-related death worldwide. Thus, developing novel therapeutic agents become urgent demands for lung cancer treatment. In this study, compound AS7128 was selected from a two-million entry chemical library screening and identified as a candidate drug that against non-small cell lung cancer (NSCLC) in vitro and in vivo. Further investigation indicated that AS7128 could induce cell apoptosis and cell cycle arrest, especially in the mitosis stage. In addition, we also found that iASPP, an oncogenic protein that functionally inhibits p53, might be associated with AS7128 through mass identification. Further exploration indicated that AS7128 treatment could restore the transactivation ability of p53 and thus increase the expressions of its downstream target genes, which are related to cell cycle arrest and apoptosis. This occurs via disruption of the interactions between p53 and iASPP in cells. Taken together, AS7128 could bind to iASPP, disrupt the interaction between iASPP and p53, and result in cell cycle arrest and apoptosis. These findings may provide new insights for using iASPP as a therapeutic target for NSCLC treatment.

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