Clitocybins, novel isoindolinone free radical scavengers, from mushroom Clitocybe aurantiaca inhibit apoptotic cell death and cellular senescence.
High concentration of intracellular reactive oxygen species (ROS) plays a role in damaging biological systems. We isolated clitocybin A from the culture broth of Clitocybe aurantiaca and then clitocybin B and C derivatives were synthesized from clitocybin A. IMR-90 lung fibroblast cells were pre-treated or post-treated with clitocybin A, B and C to the addition of 100 muM H(2)O(2). These compounds inhibited the level of intracellular reactive oxygen species (ROS) and H(2)O(2)-induced cell death as judged by hypodiploid cell formation. The inhibitory effect of clitocybins on H(2)O(2)-induced cell death was comparable to that with N-acetylcysteine (NAC), a well-known ROS scavenger. The inhibition of H(2)O(2)-induced cell death by clitocybins was mediated by the reduction of caspase 3 and 9 activation, cytochrome c release from mitochondria and the degradation of IkappaB-alpha and IkappaB-beta, which could be resulted in the prevention of cellular senescence. It suggests that clitocybins are novel compounds scavenging ROS and protect cells from apoptosis and cellular senescence.
Moon
Eun-Yi
EY
Department of Bioscience and Biotechnology, Sejong University, 98 Kunja-Dong Kwangjin-Gu, Seoul 143-747, Republic of Korea. eunyimoon@sejong.ac.kr
Oh
Jin-Mi
JM
Kim
Young-Hee
YH
Ryoo
In-Ja
IJ
Yoo
Ick-Dong
ID
D000111:Acetylcysteine / Q000494:pharmacology; D000363:Agaricales; D017209:Apoptosis / Q000187:drug effects*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D002460:Cell Line; D016922:Cellular Senescence / Q000187:drug effects*; D045304:Cytochromes c / Q000378:metabolism; D016166:Free Radical Scavengers / Q000138:chemical synthesis / Q000494:pharmacology*; D005656:Fungal Proteins / Q000138:chemical synthesis / Q000494:pharmacology*; D006801:Humans; D006861:Hydrogen Peroxide; D020672:I-kappa B Proteins / Q000378:metabolism; D054833:Isoindoles / Q000138:chemical synthesis / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D008928:Mitochondria / Q000378:metabolism; D000072000:NF-KappaB Inhibitor alpha
D016166:Free Radical Scavengers; D005656:Fungal Proteins; C083487:I kappa B beta protein; D020672:I-kappa B Proteins; D054833:Isoindoles; C000606204:NFKBIA protein, human; C535086:clitocybin A; D000072000:NF-KappaB Inhibitor alpha; C546683:clitocybin C; D045304:Cytochromes c; D006861:Hydrogen Peroxide; C546682:clitocybin B; D053148:Caspase 3; D053453:Caspase 9; D000111:Acetylcysteine