Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis

Ambrosio Hernandez, Robert Thomas, Farin Smith, Jennie Sandberg, Sunghoon Kim, Dai H. Chung, B. Mark Evers

Research output: Contribution to journalArticle

67 Citations (Scopus)

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.

Original languageEnglish (US)
Article number92089
Pages (from-to)265-272
Number of pages8
JournalSurgery
Volume130
Issue number2
DOIs
StatePublished - Jan 1 2001
Externally publishedYes

Fingerprint

Butyrates
Colonic Neoplasms
Apoptosis
Proteins
Annexin A5
Caspase 3
Cell Death
Tumor Necrosis Factor-alpha
cdc Genes
Caspase Inhibitors
Butyric Acid
Poisons
Ribonucleases
Caspases
Fluorescent Antibody Technique
Colorectal Neoplasms
Neoplasms
Therapeutics
Western Blotting
RNA

ASJC Scopus subject areas

  • Surgery

Cite this

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), 265-272. [92089]. https://doi.org/10.1067/msy.2001.115897

Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. / Hernandez, Ambrosio; Thomas, Robert; Smith, Farin; Sandberg, Jennie; Kim, Sunghoon; Chung, Dai H.; Evers, B. Mark.

In: Surgery, Vol. 130, No. 2, 92089, 01.01.2001, p. 265-272.

Research output: Contribution to journalArticle

Hernandez, A, Thomas, R, Smith, F, Sandberg, J, Kim, S, Chung, DH & Evers, BM 2001, 'Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis', Surgery, vol. 130, no. 2, 92089, pp. 265-272. https://doi.org/10.1067/msy.2001.115897
Hernandez A, Thomas R, Smith F, Sandberg J, Kim S, Chung DH et al. Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. Surgery. 2001 Jan 1;130(2):265-272. 92089. https://doi.org/10.1067/msy.2001.115897
Hernandez, Ambrosio ; Thomas, Robert ; Smith, Farin ; Sandberg, Jennie ; Kim, Sunghoon ; Chung, Dai H. ; Evers, B. Mark. / Butyrate sensitizes human colon cancer cells to TRAIL-mediated apoptosis. In: Surgery. 2001 ; Vol. 130, No. 2. pp. 265-272.
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