期刊
ANTI-CANCER DRUGS
卷 21, 期 9, 页码 850-860出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/CAD.0b013e32833e53cf
关键词
apoptosis; cell cycle arrest; colon cancer; geranylgeranylacetone; isoprenoid; p21; p27; phosphorylated retinoblastoma protein
资金
- Ministry of Education, Culture, Sports, Science and Technology of Japan
- Ministry of Health, Labor and Welfare of Japan
Geranylgeranylacetone (GGA), an isoprenoid compound, is a widely used antiulcer drug developed in Japan. GGA is structurally similar to plaunotol and geranylgeraniol, another isoprenoid reported to exert strong anticancer effects. In an earlier study, GGA was shown to inhibit ovarian cancer invasion by attenuating not only Rho activation, but also Ras-MAPK activation. In this study, we aimed to test whether GGA could have a therapeutic effect on colon cancer cells. As a result, we found that GGA induced a dose-dependent decrease in the proliferative activity through induction of cell apoptosis and cell cycle arrest in the G(1) phase. The induction of apoptosis was mediated by the activation of both caspase-8 and caspase-9 pathways. The induction of G(1) arrest was mediated by the increase of p21 and p27, and also the decrease of phosphorylated retinoblastoma protein levels. This study showed the potential anticancer activity of GGA. As this drug is already available in Japan for clinical use as an antiulcer/antigastritis agent, clinical trials will be designed to confirm its potential usefulness for cancer patients. Anti-Cancer Drugs 21:850-860 (C) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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