Title: Cyclin d1 downregulation contributes to anticancer effect of isorhapontigenin on human bladder cancer cells.
Authors: Fang, Yong; Cao, Zipeng; Hou, Qi; Ma, Chen; Yao, Chunsuo; Li, Jingxia; Wu, Xue-Ru; Huang, Chuanshu
Published In Mol Cancer Ther, (2013 Aug)
Abstract: Isorhapontigenin (ISO) is a new derivative of stilbene compound that was isolated from the Chinese herb Gnetum Cleistostachyum and has been used for treatment of bladder cancers for centuries. In our current studies, we have explored the potential inhibitory effect and molecular mechanisms underlying isorhapontigenin anticancer effects on anchorage-independent growth of human bladder cancer cell lines. We found that isorhapontigenin showed a significant inhibitory effect on human bladder cancer cell growth and was accompanied with related cell cycle G(0)-G(1) arrest as well as downregulation of cyclin D1 expression at the transcriptional level in UMUC3 and RT112 cells. Further studies identified that isorhapontigenin downregulated cyclin D1 gene transcription via inhibition of specific protein 1 (SP1) transactivation. Moreover, ectopic expression of GFP-cyclin D1 rendered UMUC3 cells resistant to induction of cell-cycle G(0)-G(1) arrest and inhibition of cancer cell anchorage-independent growth by isorhapontigenin treatment. Together, our studies show that isorhapontigenin is an active compound that mediates Gnetum Cleistostachyum's induction of cell-cycle G(0)-G(1) arrest and inhibition of cancer cell anchorage-independent growth through downregulating SP1/cyclin D1 axis in bladder cancer cells. Our studies provide a novel insight into understanding the anticancer activity of the Chinese herb Gnetum Cleistostachyum and its isolate isorhapontigenin.
PubMed ID: 23723126
MeSH Terms: Animals; Antineoplastic Agents, Phytogenic/pharmacokinetics; Antineoplastic Agents, Phytogenic/pharmacology*; Binding Sites; Cell Cycle/drug effects; Cell Line, Tumor; Cell Proliferation/drug effects; Cyclin D1/genetics*; Cyclin D1/metabolism; Disease Models, Animal; Down-Regulation; Gene Expression Regulation, Neoplastic/drug effects*; Humans; Male; Mice; Promoter Regions, Genetic; Sp1 Transcription Factor/metabolism; Stilbenes/pharmacokinetics; Stilbenes/pharmacology*; Transcription, Genetic/drug effects; Urinary Bladder Neoplasms/genetics*; Urinary Bladder Neoplasms/metabolism; Xenograft Model Antitumor Assays