Menadione (NSC 4170) Menadione (NSC 4170, Vitamin K3), a fat-soluble compound, is an inhibitor of Cdc25 phosphatase and mitochondrial DNA polymerase γ (pol γ) , used as a nutritional supplement. In vitro
Menadione prevents mitochondrial Ca(2+) uptake in normal pancreatic acinar cells, which permits rapid spread of Ca(2+) throughout the cell. Menadione-induced mitochondrial depolarisation is due to induction of the permeability transition pore. Menadione (nontoxic concentration) results in a brief activation of extracellular signal-regulated\xa0kinase (ERK) and c-Jun N-terminal kinase (JNK) in the RALA255-10G rat\xa0hepatocyte\xa0cell line. Menadione is equipotent against multidrug-resistant and parental leukemia\xa0cell\xa0lines\xa0with IC50 values of 13.5 mM and 18 mM, respectively. Menadione\xa0inhibits the incorporation of radioactive thymidine, uridine and amino acids into DNA, RNA and protein, respectively, in three\xa0humancancer cell lines. Menadione\xa0at 1-20 mM dose- and time-dependently inhibits cell proliferation of\xa0AR4-2J\xa0cells.\xa0Menadione\xa0(100 mM) causes rapid cell death. Menadione\xa0(100 mM) induces DNA smear in electrophoresis indicative of\xa0necrosis, while lower concentrations (10-20 mM) induces a DNA ladder indicative of\xa0apoptosis. Menadione\xa0at 1-20 mM induces wild-type P53, whereas the 100 mM\xa0menadione\xa0has a minor effect on wild-type P53. Menadione\xa0treatment clearly affects the mitochondrial function of Jurkat T cells by inducing a collapse of the inner transmembrane potential (DeltaPsi(m)) and a decrease in inner membrane mass, which could be completely reversed by N-acetylcysteine.
