Molecular mechanisms of apoptosis induction by 2-dodecylcyclobutanone, a radiolytic product of palmitic acid, in human lymphoma U937 cells

作者：Yu Da Yong; Zhao Qing Li; Furuta Masakazu; Todoriki Setsuko; Izumi Keisuke; Yamakage Kohji; Matsumoto Kozo; Nomura Takaharu; Kondo Takashi^*

来源：Apoptosis, 2012, 17(6): 636-645.

DOI：10.1007/s10495-012-0698-1

• 2-Dodecylcyclobutanone
• Palmitic acid
• Apoptosis
• Reactive oxygen species
• Calcium

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, -acetyl--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 from the mitochondria to the cytosol. In addition, an increase in intracellular Ca2+ concentration ([Ca2+](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 [Ca2+](i) involved in apoptosis are induced by 2-DCB and PA in U937 cells.

• 出版日期2012-6
• 单位test