Effects of the anti-inflammatory drug celecoxib on cell death signaling in human colon cancer

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 2 + -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 ( Δ Ψ m ). 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 Δ Ψ m by reducing TMEM117 expression and provide insights for the development of novel drugs through TMEM117 expression.