Deoxycholic acid induces reactive oxygen species accumulation and promotes colorectal cancer cell apoptosis through the CaMKII-Ca 2+ pathway

作者：Jiayan Chen, Jingyi Wen, Jia-Long Lin, Li Yan, Yizhang Wu, Liqin Lou, Yongliang Lou, Zhigui Zuo, Xiang Li · 发表于：World Journal of Gastrointestinal Oncology · 年份：2025 · DOI：10.4251/wjgo.v17.i8.107453 · 被引用次数：6 · 研究领域：Genomics, phytochemicals, and oxidative stress、Cholesterol and Lipid Metabolism、Eicosanoids and Hypertension Pharmacology

BACKGROUND Deoxycholic acid (DCA), a secondary bile acid, is associated with colorectal carcinogenesis, but its mechanisms remain unclear. AIM To investigate how DCA regulates apoptosis in colorectal cancer (CRC) cells. METHODS SW480 and DLD-1 CRC cell lines were used to investigate the mechanism of apoptosis by western blotting, flow cytometry, confocal microscopy, and other methods. RESULTS DCA significantly induced apoptosis, with rates increasing to 7.2% ± 1.5% in SW480 cells and 14.3% ± 0.6% in DLD-1 cells after treatment, compared to 4.7% ± 1.0% and 11.6% ± 0.8% in controls (P < 0.05). Western blot analysis showed upregulation of pro-apoptotic proteins Bax and Cleaved-PARP, with a significant increase in the Cleaved-PARP/PARP ratio (P < 0.001). DCA treatment also increased the intracellular reactive oxygen species (ROS) levels of SW480 and DLD-1 cells to 1.2-fold and 1.3-fold, respectively (P < 0.01), while the increase of mitochondrial ROS levels in these cells was statistically significant under confocal microscopy. Additionally, cytosolic and mitochondrial Ca2+ levels increased 1.3-fold and 1.2-fold, respectively, in SW480 cells (P < 0.01), and 1.1-fold and 1.1-fold, respectively, in DLD-1 cells compared with controls (P < 0.05). p-CaMKII protein levels were also elevated (P < 0.01), indicating activation of the Ca2+-CaMKII signaling pathway. Pharmacological inhibition with BAPTA-AM (1 μM) reduced mitochondrial Ca2+ accumulation and ROS levels in SW...