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 Ca2 +-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.
Keywords: Celecoxib; Endoplasmic reticulum stress; Mitochondrial membrane potential; Mitochondrial transcription factor A; Transmembrane protein 117; Uncoupling protein 2.
© 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Germany, part of Springer Nature.