Acquisition of resistance to butyrate induces resistance to luminal components and other types of stress in human colon adenocarcinoma cells.
Butyrate, naturally produced by anaerobic fermentation of diet-fiber, is the major nutrient of colonocytes and also an important regulator of colonic epithelium renewal and physiology. Other luminal components, such as bile acids or bacterial products, influence these processes. The model system we used to analyze the influence of several luminal stressors is composed of a previously established cell line resistant to the apoptotic effects of butyrate and their parental butyrate-sensitive cells. Viability of butyrate-resistant cells is unaffected by mild heat-shock (2h, 42 degrees C) and only slightly reduced by severe heat-shock (2h, 45 degrees C) in contrast to their butyrate-sensitive counterparts. The higher constitutive expression of HSP70 and HSP60 could contribute to this resistance. In addition, expression of HSP70 follows a different pattern after heat-shock in both cell lines. Butyrate-resistant cells are quite unaffected by treatment with deoxycholic acid but apoptosis is induced by chenodeoxycholic acid although to a lower extent than in butyrate-sensitive cells. These resistant cells are also less sensitive to lipopolysaccharide and show differences regarding the activation of ERK following osmotic stress. Thus, the cell model herein reported is a useful tool for investigating the molecular mechanisms of resistance to apoptosis, as well as to analyze specific targets for butyrate-resistant tumors.
Olmo
N
N
Departamento de Bioquímica y Biología Molecular I, Universidad Complutense, Madrid, Spain.
Turnay
J
J
Lecona
E
E
García-Díez
M
M
Llorente
B
B
Santiago-Gómez
A
A
Lizarbe
M A
MA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000473:pathology; D017209:Apoptosis / Q000187:drug effects; D001647:Bile Acids and Salts / Q000494:pharmacology; D002087:Butyrates / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000473:pathology; D019008:Drug Resistance, Neoplasm; D006360:Heat-Shock Proteins / Q000096:biosynthesis; D006801:Humans; D008070:Lipopolysaccharides / Q000494:pharmacology; D009997:Osmotic Pressure; D013312:Stress, Physiological
D001647:Bile Acids and Salts; D002087:Butyrates; D006360:Heat-Shock Proteins; D008070:Lipopolysaccharides