Acquisition of resistance to butyrate enhances survival after stress and induces malignancy of human colon carcinoma cells.
Acquired resistance to apoptosis by tumor cells remains a major obstacle for cancer treatment, and hence the analysis of resistance to apoptosis constitutes a major goal in the development of antitumoral drugs. We have established a butyrate-resistant human colon adenocarcinoma cell line (BCS-TC2.BR2) from nontumorigenic BCS-TC2 cells to analyze whether the acquisition of such phenotype confers resistance to apoptosis and stress. Although BCS-TC2.BR2 cells exhibited a more differentiated phenotype than the parental BCS-TC2 cells, higher butyrate concentrations remained capable of additionally enhancing their differentiation without inducing apoptosis. Survival rates of BCS-TC2.BR2 cells after glucose deprivation and heat shock were higher than those of parental cells, revealing a stress-resistant phenotype. These findings were accompanied by key differences between parental and butyrate-resistant cells in gene expression profiles and the acquisition of in vivo tumorigenicity. In conclusion, cells gaining resistance to an endogenous physiological modulator of growth, differentiation, and apoptosis concurrently acquired resistance to other agents that influence cell survival.
López de Silanes
Isabel
I
Departamento de Bioquímica y Biología Molecular, Facultad de Ciencias Químicas, Universidad Complutense, Madrid, Spain.
Olmo
Nieves
N
Turnay
Javier
J
González de Buitrago
Gonzalo
G
Pérez-Ramos
Pablo
P
Guzmán-Aránguez
Ana
A
García-Díez
Marta
M
Lecona
Emilio
E
Gorospe
Myriam
M
Lizarbe
M Antonia
MA
D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D002087:Butyrates / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D019008:Drug Resistance, Neoplasm; D020869:Gene Expression Profiling; D005947:Glucose / Q000172:deficiency; D018882:Heat Stress Disorders / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D018874:Spheroids, Cellular
D002087:Butyrates; D005947:Glucose