The nuclear receptor constitutive active/androstane receptor arrests DNA-damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase

✍ Scribed by Hiroki Kamino; Masahiko Negishi

• Book ID: 102500464
• Publisher: John Wiley and Sons
• Year: 2011
• Tongue: English
• Weight: 275 KB
• Volume: 51
• Category: Article
• ISSN: 0899-1987
• DOI: 10.1002/mc.20783

✦ Synopsis

Abstract

Here, we have demonstrated that xenobiotic activation of the nuclear receptor (CAR, NR1I3) can result in arresting DNA‐damaged human hepatocellular carcinoma Huh7 cells at the G2/M phase. Huh7 cells over‐expressing CAR were either treated with dimethyl sulfoxide, the CAR activator TCPOBOP (1,4‐bis[2‐(3,5‐dichloropyridyloxy)]benzene; androstenol, 16,(5α)‐androsten‐3α‐OL), or repressor androstenol; these treatments were then followed by adriamycin treatment to damage DNA. FACS analysis revealed that CAR‐activation by TCPOBOP increased the rate of arrested Huh7 cells at the G2/M phase (4N DNA content) after DNA damage by adriamycin. This increase correlated with the increase of cell viability in TCPOBOP‐treated Huh7 cells, as determined by MTT assays. Real‐time polymerase chain reaction analysis determined that, as regulated by CAR, the growth arrest and DNA damage‐inducible γ (GADD45γ) and Cyclin G2 genes increased and decreased, respectively, as TCPOBOP increased the number of Huh7 cells arrested at the G2/M phase. Thus, the results suggest that CAR regulates cell cycle, increasing G2/M arrest, and delaying the death of DNA‐damaged cells. Mol. Carcinog. © 2011 Wiley Periodicals, Inc.