[Proteasome inhibitors: induction of apoptosis as new therapeutic option in prostate cancer].
New perspectives in prostate cancer genesis and putative clinical management have emerged in recent years . Apoptosis plays a major role in this environment. Proteasome inhibitors block the action of a multicatalytic proteinase complex involved in the degradation of intracellular proteins, particularly with regard to cell cycle regulation and apoptosis. Numerous in vitro studies have demonstrated the ability of these compounds to induce apoptosis and enhance the activity of conventional tumoricidal agents in many cancer cell types, including prostate cancer cells. They point out the use of these potent inhibitors as a new potential molecular approach to the therapeutic management of prostate cancer. Furthermore, the action of proteasome inhibitors has been tested in animal models and in patients with hormone refractory prostate cancer, resulting in both PSA and tumor volume decrease. PS-341 (bortezomib, Velcade) is the first proteasome inhibitor with clinical application in cancer therapy that has been used in clinical trials to date. This report reviews the current status of those papers that have tried to analyze the connection between the proteasome pathway and apoptosis. We present our results of proteasome inhibition in individual prostate cancer cell lines. Proteasomal inhibition may offer a new therapeutic access in "molecular targeting" of prostate cancer.
Tahmatzopoulos
A
A
Klinik für Urologie und Kinderurologie, Universitätskliniken des Saarlandes, Homburg/Saar, Germany.
Gudegast
C
C
Stöckle
M
M
Wullich
B
B
Unteregger
G
G
Zwergel
U
U
Zwergel
T
T
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects* / Q000502:physiology; D001897:Boronic Acids / Q000494:pharmacology / Q000627:therapeutic use*; D000069286:Bortezomib; D017321:Clinical Trials, Phase I as Topic; D017322:Clinical Trials, Phase II as Topic; D006801:Humans; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009374:Neoplasms, Experimental / Q000188:drug therapy; D017430:Prostate-Specific Antigen / Q000097:blood; D011471:Prostatic Neoplasms / Q000097:blood / Q000188:drug therapy*; D011480:Protease Inhibitors / Q000627:therapeutic use*; D061988:Proteasome Inhibitors; D011719:Pyrazines / Q000627:therapeutic use*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D014409:Tumor Necrosis Factor-alpha / Q000008:administration & dosage / Q000627:therapeutic use
D000970:Antineoplastic Agents; D001897:Boronic Acids; D011480:Protease Inhibitors; D061988:Proteasome Inhibitors; D011719:Pyrazines; D014409:Tumor Necrosis Factor-alpha; D000069286:Bortezomib; D017430:Prostate-Specific Antigen