2-2--methylenebis(1-3-cyclohexanedione) and Hepatitis

M50054, 2,2'-methylenebis (1,3-cyclohexanedione), was identified as a novel inhibitor of apoptosis (programmed cell death) using an in vitro cell death assay system induced in human Fas-expressing WC8 cells by soluble human Fas ligand. Furthermore, M50054 inhibited the apoptotic cell death of U937, a human monocytic leukemic cell line, induced by anticancer agents such as etoposide; it was also confirmed that M50054 inhibited apoptotic features such as DNA fragmentation and phosphatidylserine exposure in these cells. These anti-apoptotic effects were attributable to inhibition of caspase-3 activation. Additionally, M50054 significantly inhibited anti-Fas-antibody-induced elevation of plasma alanine aminotransferase and aspartate aminotransferase. Alopecia (hair loss) symptoms were also significantly improved with topical treatment with M50054. In conclusion, M50054 inhibits apoptosis induced by a variety of stimuli via inhibition of caspase-3 activation, and may thus be effective for hepatitis and chemotherapy-induced alopecia.

Topics: Alopecia; Animals; Antineoplastic Agents; Apoptosis; Caspase 3; Caspase Inhibitors; COS Cells; Cyclohexanones; Enzyme Activation; Etoposide; Fas Ligand Protein; fas Receptor; Female; Hepatitis; Humans; Membrane Glycoproteins; Mice; Mice, Inbred BALB C; U937 Cells