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.