Deoxycholic acid induces reactive oxygen species accumulation and promotes colorectal cancer cell apoptosis through the CaMKII-Ca2+ pathway

  • World J Gastrointest Oncol. 2025 Aug 15;17(8):107453. doi: 10.4251/wjgo.v17.i8.107453.
Jia-Yan Chen  1  2 ,  Jing-Yi Wen  3 ,  Jia-Long Lin  2  4 ,  Yan Li  1  2  5 ,  Yi-Zhang Wu  2  4 ,  Li-Qin Lou  1  2 ,  Yong-Liang Lou  1  2 ,  Zhi-Gui Zuo  2  4 ,  Xiang Li  1  6
Affiliations
  • 1. Wenzhou Key Laboratory of Sanitary Microbiology, Key Laboratory of Laboratory Medicine, School of Laboratory Medicine and Life Sciences, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
  • 2. Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
  • 3. College of Chemistry and Chemical Engineering, Lanzhou University, Lanzhou 730000, Gansu Province, China.
  • 4. Department of Colorectal Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
  • 5. Renji College, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China.
  • 6. Colorectal Cancer Research Center, Wenzhou Medical University, Wenzhou 325035, Zhejiang Province, China. [email protected].
PMID: 40837770 DOI: 10.4251/wjgo.v17.i8.107453
Abstract

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 SW480 cells (P < 0.05), and suppressed Apoptosis.

Conclusion: DCA activates the CA2+-CaMKII pathway, leading to ROS-mediated Apoptosis in CRC cells, providing insights for potential therapeutic targets.

Keywords
Apoptosis; Colorectal cancer; Deoxycholic acid; Mitochondrial calcium; Reactive oxygen species.
Products