Cyclin D1 Downregulation Contributes to Anti-Cancer Effect of Isorhapontigenin (ISO) on Human Bladder Cancer Cells

• Published in: Molecular cancer therapeutics 2013-05, Vol.12 (8), p.1492-1503
• Main Authors: Fang, Yong, Cao, Zipeng, Hou, Qi, Ma, Chen, Yao, Chunsuo, Li, Jingxia, Wu, Xue-Ru, Huang, Chuanshu
• Format: Article
• Language: English
• ISSN: 1535-7163; 1538-8514
• DOI: 10.1158/1535-7163.MCT-12-0922

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 ISO anti-cancer effects on anchorage-independent growth of human bladder cancer cell lines. We found that ISO showed a significant inhibitory effect on human bladder cancer cell growth and was accompanied with related cell cycle G0/G1 arrest as well as downregulation of Cyclin D1 expression at the transcriptional level in UMUC3 and RT112 cells. Further studies identified that ISO down-regulated Cyclin D1 gene transcription via inhibition of SP1 transactivation. Moreover, ectopic expression of GFP-Cyclin D1 rendered UMUC3 cells resistant to induction of cell cycle G0/G1 arrest and inhibition of cancer cell anchorage-independent growth by ISO treatment. Together, our studies demonstrate that ISO is an active compound that mediates for Gnetum Cleistostachyum’s induction of cell cycle G0/G1 arrest and inhibition of cancer cell anchorage-independent growth through down-regulating SP1/Cyclin D1 axis in bladder cancer cells. Our studies provide a novel insight into understanding the anti-cancer activity of the Chinese herb Gnetum Cleistostachyum and its isolate ISO.