Ursodeoxycholic acid exhibits greater inhibitory effects on cancerous hct116 colon cells than on noncancerous ncm460 colon cells

Authors: Zeng, Huawei; Safratowich, Bryan; CHENG, WEN-HSING - Texas Woman'S University; BRISKE-ANDERSON, MARY - Retired ARS Employee

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 3/16/2025
Publication Date: 3/19/2025
Citation: Zeng, H., Safratowich, B.D., Cheng, W., Briske-Anderson, M. 2025. Ursodeoxycholic acid exhibits greater inhibitory effects on cancerous hct116 colon cells than on noncancerous ncm460 colon cells. Nutrients. 17(6). https://doi.org/10.3390/nu17061072.
DOI: https://doi.org/10.3390/nu17061072

Interpretive Summary: Fat consumption is associated with bile acid metabolism. In response to dietary fat, bile acids are synthesized in the liver. Subsequently, these bile acids are released from gall bladder to the small intestine for facilitating lipid absorption. Certain healthy diets increase ursodeoxycholic acid (UDCA) contents which exhibit anticancer potential. However, its anticancer mechanistic action remains largely unknown. We hypothesize that UDCA inhibits cancerous colon cell proliferation but to a lesser extent in noncancerous colon cells. In this study, we demonstrated that UDCA induces cell cycle arrest and apoptosis in cancerous HCT116 colon cells with a greater extent compared to noncancerous NCM460 colon cells These data provide further insights into the anticancer potential of UDCA against colon cancer cells and will be useful for scientists who are interested in diet and colon cancer prevention.

Technical Abstract: Scope: Ursodeoxycholic acid (UDCA), a hydrophilic bile acid, may exhibit anti-inflammatory effects and attenuate colon carcinogenesis. Certain healthy diets increase UDCA levels but its anticancer mechanistic actions remain largely unknown. We hypothesize that UDCA inhibits cancerous colon cell proliferation but to a lesser extent in noncancerous colon cells. Methods and results: Upon exposure to UDCA (0 to 0.4 mM) for 48 h, inhibition of cell proliferation, apoptosis, and cell cycle arrest were greater (> 0.9-fold) in cancerous HCT116 cells than in noncancerous NCM460 cells. In UDCA treated HCT116 cells, we identified 18 genes with = 0.8- fold change in mRNA levels out of 93 apoptosis related genes which were involved in caspase, death receptor and NF-kB pathways. At the molecular level, 0.4 mM UDCA reduced the protein level of the proto-oncogenic c-Myc gene but increased the putative tumor suppressor p21 gene (= 1-fold) via the ERK1/2/c-Myc/p21 pathway which regulates cell cycle and apoptosis. These cell data are consistent with lower c-Myc but higher p21 expression in normal colon tissues compared to cancerous colon issues. Conclusion: Collectively, UDCA inhibits cancerous colon cells but to a lesser extent in noncancerous colon cells via cell cycle and apoptosis pathways involving in ERK1/2/c-Myc/p21 signaling.