Maruyama Ryuto, Kiyohara Yuki, Kudo Yasuhiro, Sugiyama Tomoyasu
Graduate School of Bionics, Tokyo University of Technology, 1401-1 Katakura-Machi, Tokyo, Hachioji, 192-0982, Japan.
Naunyn Schmiedebergs Arch Pharmacol. 2023 Jun;396(6):1171-1185. doi: 10.1007/s00210-023-02399-4. Epub 2023 Jan 24.
The anti-inflammatory drug celecoxib, the only inhibitor of cyclooxygenase-2 (COX-2) with anticancer activity, is used to treat rheumatoid arthritis and can cause endoplasmic reticulum (ER) stress by inhibiting sarco/ER Ca-ATPase activity in cancer cells. This study aimed to investigate the correlation between celecoxib-induced ER stress and the effects of celecoxib against cell death signaling. Treatment of human colon cancer HCT116 cells with celecoxib reduced their viability and resulted in a loss of mitochondrial membrane potential ([Formula: see text]). Additionally, celecoxib treatment reduced the expression of genes involved in mitochondrial biogenesis and metabolism such as mitochondrial transcription factor A (TFAM) and uncoupling protein 2 (UCP2). Furthermore, celecoxib reduced transmembrane protein 117 (TMEM117), and RNAi-mediated knockdown of TMEM117 reduced TFAM and UCP2 expressions. These results suggest that celecoxib treatment results in the loss of [Formula: see text] by reducing TMEM117 expression and provide insights for the development of novel drugs through TMEM117 expression.
抗炎药物塞来昔布是唯一具有抗癌活性的环氧化酶-2（COX-2）抑制剂，用于治疗类风湿性关节炎，且可通过抑制癌细胞中的肌浆网/内质网Ca-ATP酶活性引发内质网（ER）应激。本研究旨在探究塞来昔布诱导的内质网应激与塞来昔布对细胞死亡信号传导影响之间的相关性。用塞来昔布处理人结肠癌HCT116细胞会降低其活力，并导致线粒体膜电位（[公式：见原文]）丧失。此外，塞来昔布处理会降低参与线粒体生物发生和代谢的基因表达，如线粒体转录因子A（TFAM）和解偶联蛋白2（UCP2）。此外，塞来昔布会降低跨膜蛋白117（TMEM117）的表达，而RNA干扰介导的TMEM117敲低会降低TFAM和UCP2的表达。这些结果表明，塞来昔布处理通过降低TMEM117表达导致[公式：见原文]丧失，并为通过TMEM117表达开发新型药物提供了思路。
