Arisostatins A induces apoptosis through the activation of caspase-3 and reactive oxygen species generation in AMC-HN-4 cells.
A microbial secondary metabolite, arisostatins A (As-A), was originally discovered as a substance carrying the antibiotic activity against Gram-positive bacteria and shown to possess potent anti-tumor properties. The mechanism by which arisostatins A initiates apoptosis remains poorly understood. In the present report we investigated the effect of arisostatins A on activation of the apoptotic pathway in HN-4 cells. Arisostatins A was shown to be responsible for the inhibition of HN-4 cell growth by inducing apoptosis. Treatment with 4 microM arisostatins A for 24h produced morphological features of apoptosis and DNA fragmentation in HN-4 cells. Arisostatins A caused dose-dependent apoptosis and DNA fragmentation of HN-4 cells used as a model. Treatment with caspase inhibitor significantly reduced the arisostatins A-induced caspase 3 activation. In addition, arisostatins A-induced apoptosis was associated with the generation of reactive oxygen species (ROS), which was prevented by an antioxidant NAC (N-acetyl-cysteine). These data indicate that cytotoxic effect of arisostatins A on HN-4 cells is attributable to the induced apoptosis and that arisostatins A-induced apoptosis is mediated by caspase-3 activation pathway, loss of mitochondrial transmembrane potential (DeltaPsi(m)), and release of cytochrome c into cytosol.
Kim
Young-Ho
YH
Department of Immunology, School of Medicine, Keimyung University, 194 DongSan-Dong Jung-Gu, Taegu 700-712, South Korea.
Shin
Ho Cheol
HC
Song
Dal Won
DW
Lee
Sung-Hee
SH
Furumai
Tamotsu
T
Park
Jong-Wook
JW
Kwon
Taeg Kyu
TK
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D053148:Caspase 3; D020169:Caspases / Q000187:drug effects / Q000378:metabolism*; D002455:Cell Division / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D019938:Cyclin D1 / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004789:Enzyme Activation / Q000187:drug effects; D006258:Head and Neck Neoplasms / Q000378:metabolism*; D018942:Macrolides; D008564:Membrane Potentials / Q000187:drug effects; D008928:Mitochondria / Q000187:drug effects; D017382:Reactive Oxygen Species / Q000819:agonists / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism
D000617:Aminoglycosides; D000900:Anti-Bacterial Agents; D000970:Antineoplastic Agents; D018942:Macrolides; D017382:Reactive Oxygen Species; C409189:arisostatin A; D019938:Cyclin D1; D053148:Caspase 3; D020169:Caspases