期刊
JOURNAL OF PHARMACOLOGY AND EXPERIMENTAL THERAPEUTICS
卷 339, 期 1, 页码 238-247出版社
AMER SOC PHARMACOLOGY EXPERIMENTAL THERAPEUTICS
DOI: 10.1124/jpet.111.181081
关键词
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资金
- Science and Technology Commission of Shanghai Municipality [09PJ1403900]
- National Natural Science Foundation of China [30800653, 81071437, 30800627]
- Fundamental Research Funds for the Central Universities
- 973 Program [2010 CB529704]
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 beta-galactosidase activity and differentiated embryo-chondrocyte expressed gene 1 expression, and blocking cell-cycle arrest in the G(1) 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, p21(WAF1/CIP1), and p16(INK4a) 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.
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