Efficacy of butyrate to inhibit colonic cancer cell growth is cell type-specific and apoptosis-dependent

Authors: ONCEL, SEMA - Oak Ridge Institute For Science And Education (ORISE); Safratowich, Bryan; LINDLAUF, JAMES - University Of North Dakota; LIU, ZHENHUA - University Of Massachusetts; PALMER, DANIEL - University Of North Dakota; Briske Anderson, Mary; Zeng, Huawei

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/9/2024
Publication Date: 2/14/2024
Citation: Oncel, S., Safratowich, B.D., Lindlauf, J., Liu, Z., Palmer, D., Briske Anderson, M.J., Zeng, H. 2024. Efficacy of butyrate to inhibit colonic cancer cell growth is cell type-specific and apoptosis-dependent. Nutrients. 16(4). Article 529. https://doi.org/10.3390/nu16040529.
DOI: https://doi.org/10.3390/nu16040529

Interpretive Summary: Colorectal cancer (CRC) is the second most common cause of cancer death in men and women in the United States. In 2023, approximately 153, 020 individuals will be di-agnosed with CRC and 52,550 will die from the disease. It has been reported that consuming high levels of dietary fiber (e.g., > 38 g / day, a male US adult) reduces the risk of colon cancer in human populations and animal models. However, the mechanism underlying this observation remains to be determined. In this study, we demonstrate that inhibitory efficacy of dietary fiber metabolites (e.g., butyrate) against human colon cancer cell proliferation is cell-type specific in a human colon cell model. The information will be useful for scientists and health-care professionals who are interested in diet and healthy gut.

Technical Abstract: Increasing dietary fiber intake is associated with reduced colon cancer risk, and this anticancer property is linked to an increased production of short chain fatty acids (e.g., butyrate). While butyrate inhibits colon cancer cell proliferation, the impact on different cancer cell types remains largely unknown. We hypothesized that butyrate exhibits different inhibitory potentials due to cancer cell type. We determined half maximal inhibitory concentrations (IC50) of butyrate in HCT116, HT-29 and Caco-2 human colon cancer cell proliferation at 24-, 48-, and 72 h, The IC50 (mM) butyrate concentrations of HCT116, HT-29, and Caco-2 were [24 h, 1.14; 48 h, 0.83; 72 h, 0.86], [24 h, N/D; 48 h, 2.42; 72 h, 2.15], and [24 h, N/D; 48 h, N/D; 72 h, 2.15], respectively. At the molecular level, butyrate inhibited cellular ERK1/2 and c-Myc survival signaling at a greater extent (> 1-fold) compared to HT-29 and Caco-2 cells. In contrast, butyrate displayed a stronger potential (> 1-fold) for inducing apoptosis and p21 tumor suppressor protein in HCT116 cells compared to HT-29 and Caco-2 cells. Moreover, a survival analysis demonstrated that a cohort with high p21 gene expres-sion in colon tissue significantly increased survival time compared to a low p21 expression cohort in colon cancer patients. Collectively, the inhibitory efficacy of butyrate is cell type specific and apoptosis dependent.