P38 MAPK protects against TNF-alpha-provoked apoptosis in LNCaP prostatic cancer cells.
OBJECTIVE
One of the most relevant aspects in cell death regulation is the signalling of apoptosis by the serine/threonine kinases MAPKs. The aim of this study was to investigate the effects of TNF-alpha stimulation on MAPK activation, and the pro- or anti-apoptotic role of these kinases in LNCaP and PC3 cells.


METHODS
Treatments were carried out using several TNF-alpha concentrations, as well as specific pharmacological inhibitors of MAPKs. Apoptosis rates were evaluated by DAPI staining and flow cytometry. MAPK phosphorylation/activation was measured by Western blot.


RESULTS
TNF-alpha induced apoptosis in a dose-dependent manner in LNCaP but not in PC3 cells. The MAPK inhibitors revealed that the apoptotic rate in LNCaP cells increased significantly following p38 inhibition. The kinase inhibitors failed to cause changes in apoptosis in PC3 cells.


CONCLUSIONS
The potentiation of apoptosis by p38 inhibition points to this kinase as a possible target for the treatment of androgen-dependent prostatic cancer.
Ricote
M
M
Departmento de Biología Celular y Genética, Universidad de Alcalá, E-28871, Alcalá de Henares, Madrid, Spain.
García-Tuñón
I
I
Fraile
B
B
Fernández
C
C
Aller
P
P
Paniagua
R
R
Royuela
M
M
D000873:Anthracenes / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D004305:Dose-Response Relationship, Drug; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism; D005419:Flavonoids / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D048031:JNK Mitogen-Activated Protein Kinases / Q000378:metabolism; D008297:Male; D011471:Prostatic Neoplasms / Q000201:enzymology / Q000378:metabolism*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D015398:Signal Transduction; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism*
D000873:Anthracenes; D005419:Flavonoids; D007093:Imidazoles; D047428:Protein Kinase Inhibitors; D011725:Pyridines; D014409:Tumor Necrosis Factor-alpha; C432165:pyrazolanthrone; D048049:Extracellular Signal-Regulated MAP Kinases; D048031:JNK Mitogen-Activated Protein Kinases; D048051:p38 Mitogen-Activated Protein Kinases; C093642:SB 203580; C093973:2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one