HPO iron chelator, CP655, causes the G1/S phase cell cycle block via p21 upregulation.

摘要: Iron is known not only for its importance in cellular and metabolic pathways but also role causing toxicities such as production of reactive oxygen species growth pathogens. The inability the human body to physiologically excrete excess iron highlights need develop a cheap yet effective chelator. This study provides initial evidence therapeutic prophylactic properties 3-hydroxypyridin-4-one (HPO) chelators murine collagen-induced arthritis. To determine whether these would be on cells, we tested panel different HPO identified 7-diethylamino-N-((5-hydroxy-6-methyl-4-oxo-1,4-dihydropyridin-3-yl)methyl)-N-methyl-2-oxo-chromen-3-carboxamide (CP655) most compound targeting CD4+ T cells. Treatment with CP655 causes significant inhibition cell proliferation inflammatory cytokines interferon-γ interleukin-17. Microarray analysis revealed dysregulation cycle-related genes following treatment. was validated by flow cytometry demonstrating G1/S phase block caused CP655. Finally, mechanistic experiments that chelator may an upregulation cycle inhibitor protein CDKN1A (p21) possible mechanism action. In conclusion, this demonstrates could prove have potential diseases driven excessive proliferation.