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Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis.
Surgery. 2001 Aug; 130(2):265-72.S

Abstract

BACKGROUND

Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a novel member of the tumor necrosis factor family, induces apoptosis in TRAIL-sensitive tumors through the activation of the caspase pathway. Sodium butyrate (NaBT) induces differentiation and apoptosis in certain colorectal cancers; the molecular mechanisms for these effects have not been clearly defined. The purpose of our study was to determine whether NaBT sensitizes TRAIL-resistant human colon cancer cells to the effects of TRAIL.

METHODS

Human colon cancer cells (KM12C, KML4A, and KM20) that are resistant to TRAIL treatment alone were treated with TRAIL (100 ng/mL), NaBT (5 mmol/L), or a combination of these agents and harvested for total RNA and protein. Western blots were performed to assess intracellular expression of Flice-like inhibitory protein (FLIP), a caspase inhibitor. Percent-specific apoptosis, relative caspase-3 activity, and Annexin-V immunofluorescence were determined at 24 and 48 hours. Cell cycle--related gene expression was assessed by RNase protection.

RESULTS

Treatment with NaBT for 24 and 48 hours decreased FLIP protein expression in all cell lines. Furthermore, NaBT sensitized these resistant cancer cells to the effects of TRAIL with significant increases noted in cell death, caspase-3 activity, and Annexin-V staining compared with NaBT alone.

CONCLUSIONS

Our findings suggest that the reduction of FLIP protein levels by NaBT renders TRAIL-resistant human colon cancer cells sensitive to TRAIL-mediated apoptosis. The combination of TRAIL with agents (such as NaBT, which target proteins that prevent cell death) may provide a more effective and less toxic regimen for the treatment of resistant colon cancers.

Authors+Show Affiliations

Department of Surgery, The University of Texas Medical Branch, Galveston, TX 77555-0536, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, U.S. Gov't, P.H.S.

Language

eng

PubMed ID

11490359

Citation

Hernandez, A, et al. "Butyrate Sensitizes Human Colon Cancer Cells to TRAIL-mediated Apoptosis." Surgery, vol. 130, no. 2, 2001, pp. 265-72.
Hernandez A, Thomas R, Smith F, et al. Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery. 2001;130(2):265-72.
Hernandez, A., Thomas, R., Smith, F., Sandberg, J., Kim, S., Chung, D. H., & Evers, B. M. (2001). Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery, 130(2), 265-72.
Hernandez A, et al. Butyrate Sensitizes Human Colon Cancer Cells to TRAIL-mediated Apoptosis. Surgery. 2001;130(2):265-72. PubMed PMID: 11490359.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. AU - Hernandez,A, AU - Thomas,R, AU - Smith,F, AU - Sandberg,J, AU - Kim,S, AU - Chung,D H, AU - Evers,B M, PY - 2001/8/8/pubmed PY - 2001/9/8/medline PY - 2001/8/8/entrez SP - 265 EP - 72 JF - Surgery JO - Surgery VL - 130 IS - 2 N2 - BACKGROUND: Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), a novel member of the tumor necrosis factor family, induces apoptosis in TRAIL-sensitive tumors through the activation of the caspase pathway. Sodium butyrate (NaBT) induces differentiation and apoptosis in certain colorectal cancers; the molecular mechanisms for these effects have not been clearly defined. The purpose of our study was to determine whether NaBT sensitizes TRAIL-resistant human colon cancer cells to the effects of TRAIL. METHODS: Human colon cancer cells (KM12C, KML4A, and KM20) that are resistant to TRAIL treatment alone were treated with TRAIL (100 ng/mL), NaBT (5 mmol/L), or a combination of these agents and harvested for total RNA and protein. Western blots were performed to assess intracellular expression of Flice-like inhibitory protein (FLIP), a caspase inhibitor. Percent-specific apoptosis, relative caspase-3 activity, and Annexin-V immunofluorescence were determined at 24 and 48 hours. Cell cycle--related gene expression was assessed by RNase protection. RESULTS: Treatment with NaBT for 24 and 48 hours decreased FLIP protein expression in all cell lines. Furthermore, NaBT sensitized these resistant cancer cells to the effects of TRAIL with significant increases noted in cell death, caspase-3 activity, and Annexin-V staining compared with NaBT alone. CONCLUSIONS: Our findings suggest that the reduction of FLIP protein levels by NaBT renders TRAIL-resistant human colon cancer cells sensitive to TRAIL-mediated apoptosis. The combination of TRAIL with agents (such as NaBT, which target proteins that prevent cell death) may provide a more effective and less toxic regimen for the treatment of resistant colon cancers. SN - 0039-6060 UR - https://www.unboundmedicine.com/medline/citation/11490359/Butyrate_sensitizes_human_colon_cancer_cells_to_TRAIL_mediated_apoptosis_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0039-6060(01)92089-6 DB - PRIME DP - Unbound Medicine ER -