PURPOSE: The purpose of the present study was to assess the biological effects of TNF-alpha in Caco-2 well-differentiated colon adenocarcinoma cells and to determine radiation sensitivity in order to develop TNF-alpha into a cancer therapeutic agent. MATERIALS AND METHODS: A cell viability test was conducted via a colorimetric and colony forming assay after 1 day and 3 days of incubation with TNF-alpha. Western blotting analysis and immunofluorescence staining were conducted to explore TNF-alpha-induced morphological and molecular changes in the adhesion molecules, E-cadherin and claudin-4. The effects of γ-irradiation at a dose of 2 Gy on cell survival were evaluated by a clonogenic assay. The molecular changes in apoptosis-regulatory proteins were assessed by Western blotting. RESULTS: Caco-2 cells were highly resistant to TNF alpha-induced cell death and 2 Gy of γ-irradiation. However, we observed the downregulation of the adherens junctional protein, E-cadherin and translocation of tight junctional protein, claudin-4 from the membrane to the cytosol induced by TNF-alpha treatment which would indicate cell-cell junction disruptions. These alterations of junctional proteins influenced the regulation of cell death in response to 2 Gy of γ-irradiation. The combined treatment of TNF-alpha with 2 Gy of γ-irradiation reduced the survival of Caco-2 cells by down-regulating bcl-xl and activating JNK pathways. CONCLUSION: These results suggest that TNF-alpha might be potentially applied as a therapeutic agent in order to enhance sensitivity to 2 Gy of γ-irradiation administered in radiotherapy for the treatment of human colon cancer.
PURPOSE: The purpose of the present study was to assess the biological effects of TNF-alpha in Caco-2 well-differentiated colon adenocarcinoma cells and to determine radiation sensitivity in order to develop TNF-alpha into a cancer therapeutic agent. MATERIALS AND METHODS: A cell viability test was conducted via a colorimetric and colony forming assay after 1 day and 3 days of incubation with TNF-alpha. Western blotting analysis and immunofluorescence staining were conducted to explore TNF-alpha-induced morphological and molecular changes in the adhesion molecules, E-cadherin and claudin-4. The effects of γ-irradiation at a dose of 2 Gy on cell survival were evaluated by a clonogenic assay. The molecular changes in apoptosis-regulatory proteins were assessed by Western blotting. RESULTS: Caco-2 cells were highly resistant to TNF alpha-induced cell death and 2 Gy of γ-irradiation. However, we observed the downregulation of the adherens junctional protein, E-cadherin and translocation of tight junctional protein, claudin-4 from the membrane to the cytosol induced by TNF-alpha treatment which would indicate cell-cell junction disruptions. These alterations of junctional proteins influenced the regulation of cell death in response to 2 Gy of γ-irradiation. The combined treatment of TNF-alpha with 2 Gy of γ-irradiation reduced the survival of Caco-2 cells by down-regulating bcl-xl and activating JNK pathways. CONCLUSION: These results suggest that TNF-alpha might be potentially applied as a therapeutic agent in order to enhance sensitivity to 2 Gy of γ-irradiation administered in radiotherapy for the treatment of humancolon cancer.
Authors: Michael A Palladino; Frances Rena Bahjat; Emmanuel A Theodorakis; Lyle L Moldawer Journal: Nat Rev Drug Discov Date: 2003-09 Impact factor: 84.694
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Authors: S Folli; A Pèlegrin; Y Chalandon; X Yao; F Buchegger; D Lienard; F Lejeune; J P Mach Journal: Int J Cancer Date: 1993-03-12 Impact factor: 7.396
Authors: V Wacheck; E Selzer; P Günsberg; T Lucas; H Meyer; C Thallinger; B P Monia; B Jansen Journal: Br J Cancer Date: 2003-10-06 Impact factor: 7.640
Authors: H Schmitz; M Fromm; C J Bentzel; P Scholz; K Detjen; J Mankertz; H Bode; H J Epple; E O Riecken; J D Schulzke Journal: J Cell Sci Date: 1999-01 Impact factor: 5.285