PT  - JOURNAL ARTICLE
AU  - Anliang Dong
AU  - Yuanzhang Fang
AU  - Li Zhang
AU  - Juan Xie
AU  - Xian Wu
AU  - Lipeng Zhang
AU  - Xiaoyuan Lian
AU  - Yihua Chen
AU  - Jian Luo
AU  - Mingyao Liu
TI  - Caffeic Acid 3,4-Dihydroxy-Phenethyl Ester Induces Cancer Cell Senescence by Suppressing Twist Expression
AID  - 10.1124/jpet.111.181081
DP  - 2011 Oct 01
TA  - Journal of Pharmacology and Experimental Therapeutics
PG  - 238--247
VI  - 339
IP  - 1
4099  - http://jpet.aspetjournals.org/content/339/1/238.short
4100  - http://jpet.aspetjournals.org/content/339/1/238.full
SO  - J Pharmacol Exp Ther2011 Oct 01; 339
AB  - Compared with traditional cytotoxic cancer therapy, therapy-induced cancer cell senescence attracts much interest because it is similarly effective, has fewer side effects, and is more efficiently cleared by immune cells. In this study, we demonstrate that unlike caffeic acid phenethyl ester, caffeic acid 3,4-dihydroxy-phenethyl ester (CADPE), which is isolated from the medicinal plants Sarcandra glabra and Teucrium pilosum, inhibits human cancer cell growth and colony formation by inducing cancer cell senescence, not apoptosis. CADPE induces cell senescence and morphology changes by increasing cellular size and cytoplasmic granularity, enhancing senescence-associated β-galactosidase activity and differentiated embryo-chondrocyte expressed gene 1 expression, and blocking cell-cycle arrest in the G1 phase. To help understand the underlying mechanisms, we show that CADPE significantly suppressed the expression of Twist1 and led to the up-regulation of rat sarcoma, p53, p21WAF1/CIP1, and p16INK4a proteins in a dose-dependent manner, resulting in the hypophosphorylation of retinoblastoma protein. Furthermore, overexpression of Twist1 prevented CADPE-induced cell senescence in tumor cells. Therefore, our studies provide evidence for a novel role of CADPE in cancer cell senescence by targeting the Twist1-dependent senescence signaling pathway.