Downregulation of Cyclin D1 by Sophorae Flos through Proteasomal Degradation in Human Colorectal Cancer Cells

Abstract

-Although Sophorae Flos (SF) has been reported to exert an anti-cancer activity, molecular targets and mechanisms associated with anti-cancer activity of SF have been unclear. Because cyclin D1 has been regarded as an important regulator in the cell proliferation, we focused cyclin D1 and investigated the effect of SF on the cyclin D1 regulation in light of elucidating the molecular mechanism for SF's anti-cancer activity. The treatment of SF decreased cellular accumulation of cyclin D1 protein. However, SF did not change the level of cyclin D1 mRNA. Inhibition of proteasomal degradation by MG132 attenuated SF-mediated cyclin D1 downregulation and the half-life of cyclin D1 was decreased in the cells treated with SF. In addition, a point mutation of threonine-286 to alanine attenuated SF-mediated cyclin D1 downregulation. Inhibition of ERK1/2 by a selective inhibitor, PD98059 suppressed cyclin D1 downregulation by SF. From these results, we suggest that SF-mediated cyclin D1 downregulation may result from proteasomal degradation through its threonine-286 phosphorylation via ERK1/2. SF-induced proteasomal degradation of cyclin D1 might inhibit proliferation in human colorectal cancer cells. The current study provides information on molecular events for an anti-cancer activity of SF

The effects and underlying mechanisms of medicine and food homologous flowers on the prevention and treatment of related diseases

“…It is currently suggested that the Sophorae Flos–mediated downregulation of cyclin D1 may be due to proteasomal degradation caused by phosphorylation of threonine 286 of extracellular regulatory protein kinases. Sophorae Flos–induced degradation of cyclin D1 proteasome may inhibit the proliferation of human colorectal cancer cells (Lee et al, 2015). Sophorae Flos extract reduces the phosphorylation of the nuclear factor κB repressor α to reduce the NF‐κB receptor activation factor ligand‐mediated induction of the NF‐κB pathway.…”