Cancer cell sensitization to fas-mediated apoptosis by sodium butyrate.
Cancer cells often resist Fas-mediated apoptosis even when the Fas receptor is expressed at the cell surface. We show here that human and rat colon cancer cells undergo massive apoptosis when they are exposed to soluble Fas ligand in the presence of sodium butyrate, an agent that induces by itself only a low rate of apoptosis. Sodium butyrate potentiates Fas-dependent apoptosis in seven out of eight colon cancer cell lines. Sodium butyrate does not increase Fas receptor cell surface expression and does not modify cell levels of Bcl-2, Bcl-xL, Bcl-xS and Bax. Sodium butyrate also induces tumor cell sensitization to the apoptotic effect of the combination of TNF-alpha and IFN-gamma, but it does not modify the level of the FADD/Mort1 adaptator molecule, at the connection between Fas- and TNF-dependent apoptosis pathways. Because the clinical toxicity of butyrate is low, its ability to enhance Fas-signal delivery in cancer cells could be of therapeutic interest.
Bonnotte
B
B
Department of Biology and Therapy of Cancer, CJF INSERM 94-8, and EPHE Faculty of Medicine, Dijon France.
Favre
N
N
Reveneau
S
S
Micheau
O
O
Droin
N
N
Garrido
C
C
Fontana
A
A
Chauffert
B
B
Solary
E
E
Martin
F
F
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D020148:Butyric Acid / Q000494:pharmacology*; D002352:Carrier Proteins / Q000378:metabolism; D003110:Colonic Neoplasms / Q000378:metabolism; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; D005434:Flow Cytometry; D006801:Humans; D020287:In Situ Nick-End Labeling; D007371:Interferon-gamma / Q000494:pharmacology; D008562:Membrane Glycoproteins / Q000235:genetics*; D008858:Microscopy, Phase-Contrast; D011518:Proto-Oncogene Proteins / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D051381:Rats; D014407:Tumor Cells, Cultured; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein
D048868:Adaptor Proteins, Signal Transducing; C494826:BAX protein, human; C494811:BCL2L1 protein, human; C494828:Bax protein, rat; C494813:Bcl2l1 protein, rat; D002352:Carrier Proteins; C505533:FADD protein, human; C505661:FASLG protein, human; C505535:Fadd protein, rat; D053222:Fas Ligand Protein; D053200:Fas-Associated Death Domain Protein; C505662:Faslg protein, rat; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D014409:Tumor Necrosis Factor-alpha; D051028:bcl-2-Associated X Protein; D051020:bcl-X Protein; D020148:Butyric Acid; D007371:Interferon-gamma