Biol. Pharm. Bull., 29(7),1335-1338, July 2006

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A Norbergenin Derivative Inhibits Neuronal Cell Damage Induced by Tunicamycin

Shinya SUZUKI,^*,a Yui OKUSE,^a Masafumi KAWASE,^a Masufumi TAKIGUCHI,^a,b Yoshiyasu FUKUYAMA,^a Hironobu TAKAHASHI,^a and Masao SATO^a

^a Faculty of Pharmaceutical Sciences, Tokushima Bunri University; 180 Yamashiro-cho, Tokushima 770-8514, Japan: and ^b Faculty of Pharmaceutical Science, Hiroshima International University; 5-1-1 Shinkai, Hiroko, Kure, Hiroshima 737-0112, Japan. * To whom correspondence should be addressed. e-mail: suzukis@ph.bunri-u.ac.jp

Several chemically synthesized compounds were examined for protective effects against the cell damage in tunicamycin-treated human neuroblastoma IMR-32 cells. Among the compounds tested, an antioxidant, Norbergenin-11-caproate (10 μM), exhibited complete protection against the cell growth inhibitory effect of tunicamycin but did not inhibit the induction of Bip/GRP78 mRNA by tunicamycin. Both norbergenin-11-caproate and α-tocopherol completely inhibited the production of reactive oxygen species induced by tunicamycin, however, α-tocopherol inhibited tunicamycin-induced cell damage only partially, even at 100 μM. These findings suggest the potential of Norbergenin-11-caproate for therapeutic application in endoplasmic reticulum (ER) stress-dependent diseases implicating a specific mechanism other than anti-oxidative one.

Key words tunicamycin; norbergenin; endoplasmic reticulum (ER) stress; antioxidant; neuroblastoma