Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells.

Isoliquiritigenin-mediated p62/SQSTM1 induction regulates apoptotic potential through attenuation of caspase-8 activation in colorectal cancer cells. Eur J Pharmacol. 2018 Oct 16;: Authors: Jin H, Seo GS, Lee SH Abstract Isoliquiritigenin (ISL) is a natural flavonoid that exhibits anticancer properties in various carcinoma cell types. However, the precise mechanism responsible for its anticancer activity has not been elucidated fully. In the present study, we examined ISL-mediated apoptotic mechanisms in colorectal cancer (CRC) cells. ISL induced apoptosis in human HCT-116 cells and caused marked induction of p62/SQSTM1 mRNA and protein expression. Similarly, ISL potently inhibited in vivo tumor growth and induced p62/SQSTM1 expression in xenograft tumor tissues. In a p62/SQSTM1 siRNA transfection study, ISL-induced p62/SQSTM1 expression attenuated ISL-mediated apoptosis by reducing caspase-8 activation. ISL potentiated the apoptotic effects of 5-fluorouracil (5-FU) on HCT-116 cells. However, ISL-induced p62/SQSTM1 expression also attenuated the potency of apoptosis induced by the combination of 5-FU and ISL. Our results demonstrate that ISL-induced p62/SQSTM1 upregulation affects ISL-mediated apoptotic potential through attenuation of caspase-8 activation in CRC cells. These findings broaden the understanding of the molecular basis of ISL-mediated apoptosis. PMID: 30339814 [PubMed - as supplied by publisher]
Source: European Journal of Pharmacology - Category: Drugs & Pharmacology Authors: Tags: Eur J Pharmacol Source Type: research