[Are mitochondria targets of anticancer drugs responsible for apoptosis?].
The vast majority of both chemical and physical anticancer treatments act through the induction of apoptotic cell death in vitro and in vivo. In numerous experimental systems, the apoptotic processes can be divided into three different phases. In the first one, multiple pro-apoptotic signal transduction pathways (e.g. P53, ROS production, etc.) are activated by various factors including anti cancer drugs. This first step is followed by an intermediate phase in which pro-apoptotic signals converge to mitochondria which in turn can finally trigger the last degradation phase of apoptosis. Consequently, mitochondria, play a pivotal role in the executive phase of apoptosis and could represent a novel attractive target for pro-apoptotic drugs. Indeed, unlike conventional anti tumour drugs which trigger pro-apoptotic signal transduction pathways upstream mitochondria, several compounds were shown to act directly on mitochondria to induce apoptosis. These drugs include betulinic acid, lonidamine, arsenic trioxide and two retinoids like CD437/AHPN and fenretinide/4-HPR. This review summarizes new data concerning these drugs targetted to mitochondria and highlights the new perspective they may offer in cancer therapy.
Marchetti
P
P
Laboratoire de biologie cellulaire, Inserm U. 459, Faculté de médecine, 1, place Verdun, 59045 Lille cedex.
Mortier
L
L
Beauvillain
V
V
Formstecher
P
P
D000818:Animals; D016588:Anticarcinogenic Agents / Q000494:pharmacology; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000502:physiology; D000077237:Arsenic Trioxide; D001152:Arsenicals / Q000494:pharmacology; D017313:Fenretinide / Q000494:pharmacology; D006801:Humans; D007191:Indazoles / Q000494:pharmacology; D008928:Mitochondria / Q000187:drug effects* / Q000378:metabolism; D009368:Neoplasm Transplantation; D009369:Neoplasms / Q000188:drug therapy*; D010087:Oxides / Q000494:pharmacology; D053978:Pentacyclic Triterpenes; D012176:Retinoids / Q000494:pharmacology; D014315:Triterpenes / Q000494:pharmacology; D000094062:Betulinic Acid
D016588:Anticarcinogenic Agents; D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D001152:Arsenicals; C099555:CD 437; D007191:Indazoles; D010087:Oxides; D053978:Pentacyclic Triterpenes; D012176:Retinoids; D014315:Triterpenes; D017313:Fenretinide; D000077237:Arsenic Trioxide; C016371:lonidamine; D000094062:Betulinic Acid