Menadione (Vitamin K3)

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. ^[1] Menadione (nontoxic concentration) results in a brief activation of extracellular signal-regulated kinase (ERK) and c-Jun N-terminal kinase (JNK) in the RALA255-10G rat hepatocyte cell line. ^[2] Menadione is equipotent against multidrug-resistant and parental leukemia cell lines with IC50 values of 13.5 mM and 18 mM, respectively. Menadione inhibits the incorporation of radioactive thymidine, uridine and amino acids into DNA, RNA and protein, respectively, in three humancancer cell lines. ^[3] Menadione at 1-20 mM dose- and time-dependently inhibits cell proliferation of AR4-2J cells. Menadione (100 mM) causes rapid cell death. Menadione (100 mM) induces DNA smear in electrophoresis indicative of necrosis, while lower concentrations (10-20 mM) induces a DNA ladder indicative of apoptosis. Menadione at 1-20 mM induces wild-type P53, whereas the 100 mM menadione has a minor effect on wild-type P53. ^[4] Menadione treatment 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. ^[5]