Kaga Chiaki, Okochi Mina, Nakanishi Mari, Hayashi Hiroki, Kato Ryuji, Honda Hiroyuki
Department of Biotechnology, School of Engineering, Nagoya University, Furo-cho, Chikusa-ku, Nagoya 464-8603, Japan.
Biochem Biophys Res Commun. 2007 Nov 3;362(4):1063-8. doi: 10.1016/j.bbrc.2007.08.110. Epub 2007 Aug 28.
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is known to induce apoptosis to various tumor cells but not in normal cells. We have screened cell death-inducing peptides from the extracellular domain sequence of TRAIL, using a peptide array. Peptides of higher activity were found through amino acid substitution, and the CNSCWSKD peptide induced >90% cell death in treated Jurkat cells. Features of apoptosis, such as DNA fragmentation, activation of caspase, phosphatidylserine externalization, chromatin condensation, and competition with TRAIL for binding to the death receptor (DR) 4 or DR5 were observed, suggesting that this peptide is a TRAIL mimic. Caspase-3 activation was observed in various tumor cells treated with this peptide as well as with TRAIL, while no activation was observed in human normal fibroblasts. The CNSCWSKD peptide is a potential candidate for use in cancer therapy.
肿瘤坏死因子相关凋亡诱导配体（TRAIL）已知可诱导多种肿瘤细胞凋亡，但对正常细胞无此作用。我们使用肽阵列从TRAIL的细胞外结构域序列中筛选诱导细胞死亡的肽。通过氨基酸替换发现了活性更高的肽，并且CNSCWSKD肽在处理的Jurkat细胞中诱导了>90%的细胞死亡。观察到凋亡的特征，如DNA片段化、半胱天冬酶激活、磷脂酰丝氨酸外翻、染色质浓缩，以及与TRAIL竞争结合死亡受体（DR）4或DR5，这表明该肽是一种TRAIL模拟物。在用该肽以及TRAIL处理的各种肿瘤细胞中均观察到半胱天冬酶-3激活，而在人正常成纤维细胞中未观察到激活。CNSCWSKD肽是癌症治疗的潜在候选物。
