表征具有不同 p53 状态的肺癌细胞中 PRIMA-1 衍生物触发的神经鞘磷脂酶途径。
Characterizing the sphingomyelinase pathway triggered by PRIMA-1 derivatives in lung cancer cells with differing p53 status.
机构信息
Department of Chemistry and Biochemistry, Konneker Research Laboratories, Ohio University, The Ridges-Ohio University, Athens, OH, U.S.A.
出版信息
Anticancer Res. 2014 Jul;34(7):3271-83.
BACKGROUND/AIM: Derivatives of PRIMA-1 compound, 8a and 8b have been shown to increase cytotoxicity in lung cancer cells through sphingomyelinase pathways in IR and 8a or 8b co-treated lung cancer cells. The goal of the present study was to further elaborate the molecular mechanism of 8a- or 8b-treated lung cancer cells in order to understand their potential as anti-cancer drugs.
MATERIALS AND METHODS
Biochemical assays, western blot, flow cytometry and gene array analyses were employed to distinguish these mechanisms.
RESULTS
Herein we demonstrated that 8a and 8b cause apoptosis with S-phase arrest in lung cancer cells by activating neutral sphingomyelinase with ceramide production. 8a induces expression of TNF family genes while 8b induces p53-mediated apoptosis genes. Protein analysis shows an increased expression in caspase 8, bcl-2, bax, caspase 9 and cytochrome c.
CONCLUSION
PRIMA-1 derivatives provoke cytotoxicity in lung cancer cells mainly through the neutral sphingomyelinase-dependent apoptosis pathway.
背景/目的：PRIMA-1 化合物的衍生物 8a 和 8b 通过 IR 中的鞘磷脂酶途径和 8a 或 8b 共同处理的肺癌细胞增加肺癌细胞的细胞毒性。本研究的目的是进一步阐述 8a 或 8b 处理的肺癌细胞的分子机制，以了解它们作为抗癌药物的潜力。
材料和方法
采用生化分析、western blot、流式细胞术和基因芯片分析来区分这些机制。
结果
本文证明 8a 和 8b 通过激活中性鞘磷脂酶产生神经酰胺导致肺癌细胞凋亡和 S 期停滞。8a 诱导肿瘤坏死因子家族基因的表达，而 8b 诱导 p53 介导的凋亡基因的表达。蛋白分析显示半胱天冬酶 8、bcl-2、bax、半胱天冬酶 9 和细胞色素 c 的表达增加。
结论
PRIMA-1 衍生物主要通过中性鞘磷脂酶依赖性凋亡途径引起肺癌细胞的细胞毒性。
Zotero 插件