Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic product of palmitic acid, in human lymphoma U937 cells.
The irradiation of fat-containing food forms 2-dodecylcyclobutanone (2-DCB) from palmitic acid (PA). In this study, we investigated whether 2-DCB and PA induce apoptosis in human lymphoma U937 cells. We found that cell viability decreased by 2-DCB and apoptosis was induced by 2-DCB and PA. 2-DCB and PA significantly enhanced the formation of intracellular reactive oxygen species (ROS). Apoptosis induced by 2-DCB and PA was strongly prevented by an antioxidant, N-acetyl-L: -cysteine. The treatment with 2-DCB and PA resulted in the loss of mitochondrial membrane potential, and Fas, caspase-8 and caspase-3 activation. Pretreatment with a pan-caspase inhibitor (z-VAD) significantly inhibited apoptosis induced by 2-DCB and PA. Moreover, 2-DCB and PA also induced Bax up-regulation, the reduction in Bcl-2 expression level, Bid cleavage and the release of cytochrome c from the mitochondria to the cytosol. In addition, an increase in intracellular Ca(2+) concentration ([Ca(2+)](i)) was observed after the treatment with 2-DCB and PA. Our results indicated that intracellular ROS generation, the modulation of the Fas-mitochondrion-caspase-dependent pathway and the increase in [Ca(2+)](i) involved in apoptosis are induced by 2-DCB and PA in U937 cells.
Department of Radiological Sciences, Graduate School of Medicine and Pharmaceutical Sciences, University of Toyama, Sugitani 2630, Toyama, Japan.
Da-Yong
DY
Yu
Qing-Li
QL
Zhao
Masakazu
M
Furuta
Setsuko
S
Todoriki
Keisuke
K
Izumi
Kohji
K
Yamakage
Kozo
K
Matsumoto
Takaharu
T
Nomura
Takashi
T
Kondo
D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000378:metabolism; D002470:Cell Survival / Q000187:drug effects; D003503:Cyclobutanes / Q000633:toxicity*; D045304:Cytochromes c / Q000378:metabolism; D005514:Food Irradiation / Q000009:adverse effects*; D005786:Gene Expression Regulation / Q000187:drug effects; D006801:Humans; D008928:Mitochondria / Q000378:metabolism; D019308:Palmitic Acid / Q000737:chemistry*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism; D020298:U937 Cells; D051028:bcl-2-Associated X Protein / Q000235:genetics / Q000378:metabolism
D003503:Cyclobutanes; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D051028:bcl-2-Associated X Protein; D019308:Palmitic Acid; D045304:Cytochromes c; C063381:2-dodecylcyclobutanone; D002118:Calcium