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

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

  • Eur J Pharmacol. 2001 Dec 14;433(1):37-45. doi: 10.1016/s0014-2999(01)01489-3.
T Tsuda 1 Y Ohmori H Muramatsu Y Hosaka K Takiguchi F Saitoh K Kato K Nakayama N Nakamura S Nagata H Mochizuki
Affiliations

Affiliation

  • 1 Research Center, Mochida Pharmaceutical Co., Ltd., 722 Jimba-aza-Uenohara, Gotemba, Shizuoka 412-8524, Japan. [email protected]
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.

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