Inhibitory effect of M50054, a novel inhibitor of apoptosis, on anti-Fas-antibody-induced hepatitis and chemotherapy-induced alopecia.

Abstract	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.
Authors	T Tsuda, Y Ohmori, H Muramatsu, Y Hosaka, K Takiguchi, F Saitoh, K Kato, K Nakayama, N Nakamura, S Nagata, H Mochizuki
Journal	European journal of pharmacology (Eur J Pharmacol) Vol. 433 Issue 1 Pg. 37-45 (Dec 14 2001) ISSN: 0014-2999 [Print] Netherlands
PMID	11755132 (Publication Type: Journal Article)
Chemical References	2,2'-methylenebis(1,3-cyclohexanedione) Antineoplastic Agents Caspase Inhibitors Cyclohexanones FASLG protein, human Fas Ligand Protein Fasl protein, mouse Membrane Glycoproteins fas Receptor Etoposide CASP3 protein, human Casp3 protein, mouse Caspase 3
Topics	Alopecia (chemically induced, drug therapy) Animals Antineoplastic Agents (toxicity) Apoptosis (drug effects) COS Cells Caspase 3 Caspase Inhibitors Cyclohexanones (pharmacology) Enzyme Activation (drug effects) Etoposide (toxicity) Fas Ligand Protein Female Hepatitis (drug therapy) Humans Membrane Glycoproteins (pharmacology) Mice Mice, Inbred BALB C U937 Cells fas Receptor (physiology)

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