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Topical Area: Diet and Cancer

Diet and Cancer (Poster Session)

(P13-048-23) Ursodeoxycholic Acid Induces Cell Cycle Arrest and Apoptosis in Cancerous HCT116 Colon Cells but to a Lesser Extent in Noncancerous NCM460 Colon Cells

Sunday, July 23, 2023
12:45 PM – 1:45 PM ET
Location: Poster Board 273

    Presenting Author(s)

  • HZ

    Huawei Zeng, PhD

    Research Molecular Biologist
    USDA-ARS Grand Forks Human Nutrition Research Center
    Grand forks, North Dakota, United States

    • Co-Author(s)

  • BS

    Bryan D. Safratowich, M. Sc.

    USDA-ARS, Grand Forks Human Nutrition Research Center
    Grand Forks, North Dakota, United States

  • WC

    Wen-Hsing Cheng, Ph.D.

    Professor
    Mississippi State University
    Mississippi State, Mississippi, United States

  • MB

    Mary Briske-Anderson, M. Sc.

    USDA-ARS, Grand Forks Human Nutrition Research Center
    Grand Forks, North Dakota, United States

Disclosure(s):
Huawei Zeng, PhD: No relevant financial relationship(s) with ineligible companies to disclose.


Objectives: Ursodeoxycholic acid (UDCA), a hydrophilic secondary bile acid and microbial metabolite in the colon, exhibits an anti-inflammatory potential and attenuates colon carcinogenesis. However, the mechanistic action of UDCA at the cellular level remains to be determined. We hypothesize that, in the colon, UDCA selectively inhibits cancerous cell proliferation through signaling pathways regulating cell cycle and apoptosis.

Methods: With human cancerous HCT116 colon cell and non-cancerous NCM460 colon cell culture models, we used cell cycle, apoptosis, PCR array, biochemical, western blotting and immunofluorescent assays to determine impacts of UDCA treatment on cell proliferation and the underlying molecular actions.

Results: Upon exposure to UDCA (0.4 mmol/L) for 48 hours, cell proliferation was reduced (p < 0.001) by 59% in HCT116 cells compared to 31% (p < 0.01) in NCM460 cells. Similarly, UDCA exhibited > 1-fold stronger (p < 0.01) potential for inducing apoptosis and cell cycle arrest at the G1 phase (concomitantly with a drop in S-phase fraction) in HCT116 cells than that in NCM460 cells. Using PCR array analysis, we identified 10 pro-apoptotic genes, 6 anti-apoptotic genes and 2 cellular mediator genes with ≥ 0.8-fold (p < 0.05) increase or decrease in mRNA levels in UDCA-treated HCT116 cells compared with untreated cells. Furthermore, UDCA treatment increased (p < 0.05) p21 tumor suppressor protein but downregulated (p < 0.05) survival signals including oncogenic cMyc protein and phosphorylation of extracellular-regulated kinase 1/2 protein in HCT116 cells.

Conclusions: In a cell culture model, UDCA inhibits cancerous HCT116 colon cell proliferation but to a lesser extent in noncancerous NCM460 colon cells via cell cycle and apoptosis pathways.

Funding Sources: U.S. Department of Agriculture, Agricultural Research Service, research project 3062-51000-056-00D.