Table 1.
Combination therapy with synthetic agents and TRAIL for improving TRAIL-mediated apoptosis in TRAIL-resistance cells.
| Agent | Cancer | Results | Ref |
|---|---|---|---|
| Entinostat | Colon cancer | Up-regulation of DR4/5 in DLD-1 and WiDr cells (in vitro) | (84) |
| Entinostat | Melanoma | Up-regulation of DR4/5 and activation of caspase 8 (in vitro) | (85) |
| SAHA | MM | Induction of caspase-8 and -9 activation in OPM-2, RPMI 8226, NCI-H929, U266, and JJN-3 cells (in vitro) | (86) |
| SAHA | Sarcoma | Attenuating mitochondrial membrane potential and caspase-3, -6, and -7 activation, and PARP cleavage in MES-SA and ESS-1 cells (in vitro) | (87) |
| VPA | ATC | Activation of JNK and the phosphorylation of FADD and c-Jun, and induction of caspase-3, and -8 activation in ARO cells (in vitro) | (88) |
| VPA | HNC | HDAC4 degradation (in vitro) | (88) |
| 5-FU | Colon cancer | Induction of caspase 3 activation and Bax expression in DLD-1 cells (in vitro) | (89) |
| 5-FU | RCC | Up-regulating p53 and Bax expression in Caki-1 cells (in vitro) | (90) |
| Cis-platin | HCC | Up-regulating DR4 (in vitro) | (91) |
| Cis-platin | Glioblastoma | Up-regulation of DR5 and down-regulation of c-FLIP in glioblastoma-derived stem cells (in vitro) | (92) |
| Cis-platin | Ovarian cancers | Up-regulating caspase-8 and DR5 expression in SKOV-3 and TOV-21G cells (in vitro) | (93) |
| Bortezomib | Gastric cancer | ERK1/2 activation resulted in DR5 up-regulation, and activation of caspases-8, -9, and -3 in SNU-216 cells (in vitro) | (94) |
| Bortezomib | MM | Up-regulating DR5 (in vitro) | (99) |
| Doxorubicin | Breast cancer | DR5 activating (in vitro and in vivo) | (100) |
| Gemcitabine | Pancreatic cancer | Elevating the expression of 4E-BP1 (in vitro) | (98) |
| Paxiline | Glioma | Down-regulating c-FLIP, an survivin expression, and up-regulating CHOP mediated DR5 expression in U251MG cells (in vitro) | (82) |
| SHetA2 | Lung cancer | Down-regulating c-FLIP, and up-regulating DR5 (in vitro) | (101) |
| Actinomycin D | Prostate cancer | Down‐regulation of XIAP, c-FLIP, Bcl-2, and up-regulation of DR4/5 in CL‐1, DU‐145, and PC‐3 cells (in vitro) | (102) |
| Actinomycin D | Pancreatic cancer | Down-regulating c-FLIP in HPAF, Panc1, Miapaca2, Bxpc3, Panc89, SW979, and Aspc1 cells (in vitro) | (103) |
| Actinomycin D | NSCLC | Increased expression of DR5 and caspase activation (in vitro and in vivo) | (104) |
| PPARy ligands | Prostate cancer | Down-regulating c-FLIP in prostate cancer, PPC-1 and LNCaP, ovarian cancer, OVCAR-3, and SK-OV-3 cells (in vitro) | (105) |
| Ovarian cancer | |||
| YM155 | Cervical cancer | Downregulation of cFLIP and surviving in HeLa cells (in vitro) | (106) |
| YM155 | Breast cancer | The p38 MAPK- and CHOP-mediated DR5 up-regulation (in vitro and in vivo) | (107) |
| YM155 | RCC | Down-regulation of Mcl-1 and NF-κB-mediated down-regulation of c-FLIP expression in Caki cells (in vitro) | (108) |
| Triciribine | Prostate cancer | Dow-regulating Akt pathway in PC-3 and LNCaP cells (in vitro) | (109) |
| PBOX | Leukemia | Up-regulation of DR5, reduction of cellular mitochondrial potential, activation of the caspase cascade, and down-regulation of PI3K/Akt, c-FLIP, Mcl-1, and IAP survival pathways (in vitro) | (110) |
| SNX-2112 | Cervical cancers | Inducing ROS-mediated JNK-p53-autophagy-DR5 pathway, and down-regulating Bcl-2, Bcl-xL, and c-FLIP in HeLa cells (in vitro) | (111) |
| Progesterone | Ovarian cancers | Down-regulating c-FLIP in OVCA 420, OVCA 429, and OVCA 433 cells (in vitro) | (112) |
| ABT-737 | Various cancers | Up-regulation of DR5 (in vitro) | (113) |
| ZFL | RCC | Downregulation of Bcl-2 and Cbl-mediated c-FLIP by ROS-mediated p53 expression in Caki cells (in vitro) | (114) |
| Bortezomib | MM | Down-regulating c-FLIP (in vitro) | (115) |
| RCC | |||
| c-Met inhibitor | Liposarcoma | Up-regulation of DR5 in patient-derived cells (PDCs) (in vitro) | (116) |
| Vemurafenib | ATC | Dow-regulating Akt pathway in C643, CAL62, HTh7 cells (in vitro) | (117) |
| Birinapant | Breast cancers | Down-regulating c-FLIP in MDA-MB-453 cell (in vitro) | (118) |
| ABC294640 | NSCLC | Up-regulating DR4/5, and inducing caspase-3, -8 expression (in vitro) | (119) |
| Docetaxel | Prostate cancers | Inducing ER stress in DU145 and PC3 cells (in vitro) | (120) |
| Cabazitaxel |
TRAIL, Tumor necrosis factor–related apoptosis-inducing ligand; DR4/5, Death receptor 4/5; PARP, Poly(ADP-ribose) Polymerase; JNK, Jun N-terminal kinase; FADD, Fas -associated death domain protein; HDAC4, Histone deacetylase 4; c-FLIP, Cellular FLICE (FADD-like IL-1β-converting enzyme)-inhibitory protein; ERK1/2, Extracellular signal–regulated protein kinase 1/2; 4E-BP1, Eukaryotic translation initiation factor 4E-binding protein 1; CHOP, C/EBP homologous protein; XIAP, X-linked inhibitor of apoptosis protein; NF-κB, Nuclear factor kappa B; Bcl-2, B-cell lymphoma-2; Bcl-xL, B-cell lymphoma-extra large; PI3K/AKT, Phosphatidylinositol 3-kinase; Bax, Bcl-2 associated X; Mcl-1, Myeloid-cell leukemia 1; Cbl, Casitas B-lineage lymphoma; ROS, Reactive oxygen species; (ER) stress, Endoplasmic reticulum; MM, Multiple myeloma; HNC, Head and neck cancer; RCC, Renal cell carcinoma; ATC, Anaplastic thyroid cancer; HCC, Hepatocellular carcinoma; NSCLC, Non-small cell lung cancer; SAHA, Suberoylanilide hydroxamic acid; VPA, Valporate; 5-FU, Fluorouracil; YM155, Sepantronium bromide; PBOX, Pyrrolo-1,5-benzoxazepine.