Table 2.
Agents known to inhibit c-FLIP expression by post-transcriptional mechanisms.
| Mechanism of action | Agent | References |
|---|---|---|
| Blockade of mRNA translation and RNaseH-mediated cleavage, with subsequent degradation of the mRNA:antisense DNA heteroduplex | Antisense oligonucleotide | [60] |
| c-FLIP RNA interference | SiRNAs | [24,45,116, 165,166] |
| Inhibitor of mammalian target of rapamycin (mTOR) | Rapamycin | [83] |
| Inhibitor of phosphorylation of (Roc) translation initiation factor 4E (eIF4E) Disrupts the eIF4E/eIF4G association | Rocaglamide | [87] |
| Antimicrotubule agent | Taxol (paclitaxel) | [7] |
| Protein synthesis inhibitors | Cyclohexamide and anisomycin | [167] |
| RNA synthesis inhibitor | Actinomycin D | [168,169] |
| Thymidylate synthase (TS) inhibitor | 5-fluorouracil (5-FU) | [8,122] |
| PPARγ modulation | CDDO, 15-deoxy-δ (12,14)-prostaglandin J2 (15d-PGJ2), Rosiglitazone, Troglitazone | [170-174] |
| Proteasome inhibitors | PS-34 (bortezomib), MG-132 | [80,175-186] |
| Bcr-Abl kinase inhibitor | Imatinib mesylate | [187,188] |
| Blocks the activation of NF-κB and TGF-β1/Smad signaling pathways | Silibinin (flavonoid) | [189] |
| Induces cyclin D1 phosphorylation, Increases ubiquitination of c-FLIP | SHetA2 | [190] |
| Akt and NF-κB downregulation | Genistin (isoflavone) | [191] |
| Multikinase inhibitor | Sorafenib | [192] |
| Inhibitor of AKT phosphorylation | Eupatolide | [193] |
| Elevation of c-Jun N-terminal kinase (JNK) and its substrate c-Jun | α-TEA | [194,195] |
| Inhibitor of transglutaminase 2 (TG2) | Cystamine | [196] |
| Proteasome-mediated degradation of c-FLIPS | Paxilline | [197] |
| Inhibitor of phosphorylation of AKT (pAKT) and cellular FLICE-like inhibitory protein (c-FLIP) | Tamoxifen | [198] |
| Increases reactive oxygen species (ROS) and induces proteasome-dependent degradation of c-FLIP | Isoquinoline alkaloid, Berberine (BBR) | [199] |
| Activator of signal transduction cascades | INF-γ | [200] |
| Induce ROS, activator of both death receptor- and mitochondrial-mediated apoptotic pathways | β-elemene piperazine derivatives | [201] |
| EGFR tyrosine kinase inhibitor | AG1478 | [202] |
| Down-regulates STAT3 | Kahweol, a coffee-specific diterpene | [203] |
| Phosphodiesterase inhibitor | Pentoxifylline (PTX) | [204] |
| Phosphatidylinositol 3′-kinase inhibitor | LY294002 | [205] |