TRAIL and chemotherapeutic drugs in cancer therapy.
Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL/Apo2L) is a recently identified member of the TNF ligand family that selectively induces apoptosis in tumor cells in vitro and in vivo but not in most normal cells. Chemotherapeutic drugs induce apoptosis and the upregulation of death receptors or activation of intracellular signaling pathways of TRAIL. Numerous chemotherapeutic drugs have been shown to sensitize tumor cells to TRAIL-mediated apoptosis. Studies from our laboratory have also shown that TRAIL-resistant renal cell carcinoma, prostate gland cancer, and bladder cancer cells are sensitized by subtoxic concentrations of chemotherapeutic drugs including doxorubicin, epirubicin, pirarubicin, and cisplatin. TRAIL, particularly in combination with chemotherapeutic agents, is thus potentially promising in the treatment of cancer. This review addresses the putative role of TRAIL in cancer treatment and discusses the molecular basis of the synergistic effect of TRAIL and chemotherapeutic drugs.
Wu
Xiu-Xian
XX
Department of Urology, Kagawa University, Kagawa 761-0793, Japan.
Ogawa
Osamu
O
Kakehi
Yoshiyuki
Y
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins / Q000378:metabolism; D053181:Caspase 8; D020169:Caspases / Q000378:metabolism; D003602:Cytotoxicity, Immunologic; D004357:Drug Synergism; D053200:Fas-Associated Death Domain Protein; D006801:Humans; D008562:Membrane Glycoproteins / Q000502:physiology / Q000627:therapeutic use; D009369:Neoplasms / Q000188:drug therapy*; D018124:Receptors, Tumor Necrosis Factor; D015398:Signal Transduction; D053221:TNF-Related Apoptosis-Inducing Ligand; D014409:Tumor Necrosis Factor-alpha / Q000502:physiology / Q000627:therapeutic use
D048868:Adaptor Proteins, Signal Transducing; D000970:Antineoplastic Agents; D051017:Apoptosis Regulatory Proteins; D002352:Carrier Proteins; C505533:FADD protein, human; D053200:Fas-Associated Death Domain Protein; D008562:Membrane Glycoproteins; D018124:Receptors, Tumor Necrosis Factor; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D014409:Tumor Necrosis Factor-alpha; C505530:CASP8 protein, human; D053181:Caspase 8; D020169:Caspases