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

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 Ca(2+) 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 Ca(2+)-CaMKII signaling pathway. Pharmacological inhibition with BAPTA-AM (1 μM) reduced mitochondrial Ca(2+) accumulation and ROS levels in SW480 cells (P < 0.05), and suppressed apoptosis. CONCLUSION: DCA activates the Ca(2+)-CaMKII pathway, leading to ROS-mediated apoptosis in CRC cells, providing insights for potential therapeutic targets.