Butyrate-induced cell death and differentiation are associated with distinct patterns of ROS in HT29-derived human colon cancer cells.
To investigate the role of reactive oxygen species (ROS) induced by butyrate in tumor cells, we compared HT29R, an HT29-derived human colon cancer cell line refractory to butyrate-induced cell differentiation but highly sensitive to cell death, with the differentiation-positive HT29-12 and HT29-21 cell lines (exhibiting low sensitivity to butyrate-induced cell death), with respect to levels of butyrate-induced free radicals (FRs), ROS, and H(2)O(2). Dose-dependent increase of FRs (as determined by electron spin resonance spectroscopy) and ROS (dichlorofluorescein assay) was induced in HT29R, but not in HT29-12 and HT29-21 cells, where, in contrast to HT29R, a dose-dependent increase of H(2)O(2) release (phenol red assay) was induced by butyrate. The mode of butyrate-induced cell death in HT29R cells was of a mixed type with necrosis predominating, which, however, switched to apoptosis as the major type of cell death in the presence of the drugs 1,5-dihydroxyisoquinoline, resveratrol, or cyclosporine A. The results suggest that FRs and ROS induced by butyrate in HT29R cells are products of cell death, while H(2)O(2) induced in HT29-12 and HT29-21 cells is functionally related to cell differentiation.
Domokos
Monika
M
Institute of Physiology and Biochemistry, Faculty of Veterinary Sciences, Szent Istvan University, Istvan u. 2, 1078, Budapest, Hungary.
Jakus
Judit
J
Szeker
Krisztina
K
Csizinszky
Rita
R
Csiko
György
G
Neogrady
Zsuzsanna
Z
Csordas
Adam
A
Galfi
Peter
P
D000975:Antioxidants / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D002087:Butyrates / Q000494:pharmacology*; D002448:Cell Adhesion / Q000187:drug effects; D016923:Cell Death / Q000187:drug effects*; D002454:Cell Differentiation / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D016572:Cyclosporine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004578:Electron Spin Resonance Spectroscopy; D005609:Free Radicals; D019073:HT29 Cells; D006801:Humans; D006861:Hydrogen Peroxide / Q000378:metabolism; D007166:Immunosuppressive Agents / Q000494:pharmacology; D020287:In Situ Nick-End Labeling; D007546:Isoquinolines / Q000494:pharmacology; D009336:Necrosis; D017382:Reactive Oxygen Species / Q000378:metabolism*; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology
D000975:Antioxidants; D002087:Butyrates; D005609:Free Radicals; D007166:Immunosuppressive Agents; D007546:Isoquinolines; D017382:Reactive Oxygen Species; D013267:Stilbenes; C095653:1,5-dihydroxyisoquinoline; D016572:Cyclosporine; D006861:Hydrogen Peroxide; D000077185:Resveratrol