Table 2.
Apoptotic associated genes validated by real-time PCR as up- or down-regulated in NCI-H460 cells following PAC treatment.
| Up-Regulated by PAC Treatment (>2.0 fold) | |||
|---|---|---|---|
| Gene | Name | Fold-Change | Function |
| BCL2L10 | BCL2-like 10 (apoptosis facilitator) | +3.25 | Anti-apoptotic member of the Bcl-2 family that blocks apoptosis in the mitochondrial death pathway, but not in the death receptor pathway [42]. |
| BID | BH3 interacting domain death agonist | +3.25 | Pro-apoptotic member of Bcl-2 proteins and encodes a death agonist that heterodimerizes with either agonist BAX or antagonist BCL2. |
| DFFA | DNA fragmentation factor | +2.00 | A substrate for caspase-3 and triggers DNA fragmentation during apoptosis [43]. |
| MCL1 | myeloid cell leukemia sequence 1 (BCL2-related) | +2.00 | Involved in the regulation of apoptosis versus cell survival and maintenance of viability, but not of proliferation. Two isoforms have been identified, isoform 1 inhibits apoptosis and isoform 2 promotes apoptosis [44]. |
| TNF | tumor necrosis factor | +9.19 | Cytokine that binds to TNFRSF1A/TNFR1 and TNFRSF1B/TNFBR, involved in the regulation cell proliferation, differentiation, apoptosis, lipid metabolism, and coagulation. Induces cell death of certain tumor cell lines. |
| TNFRSF10A | tumor necrosis factor receptor superfamily, member 10a | +3.03 | Transduces cell death signal and induces cell apoptosis via activation by tumor necrosis factor-related apoptosis inducing ligand (TNFSF10/TRAIL) [45]. |
| TNFRSF25 | tumor necrosis factor receptor superfamily, member 25 | +14.93 | TNFSF12/APO3L/TWEAK receptor, interacts directly with the TRADD, mediates activation of NF-kappa-B and induces apoptosis [46)]. |
| TNFSF7 | tumor necrosis factor receptor superfamily, member 7 | +2.83 | Cytokine that binds to CD27 and involved in T-cell activation. Induces proliferation of co-stimulated T-cells and enhances the generation of cytolytic T-cells [47]. |
| TP73 | tumor protein P73 | +22.63 | Postulated tumor suppressor protein and p53 family member. Family members include p53, p63, and p73 and have high sequence similarity, which allows p63 and p73 to transactivate p53-responsive genes causing cell cycle arrest and apoptosis. [33]. |
| TRADD | TNFRSF1A-associated via death domain | +12.13 | Adaptor molecule that interacts with TNFRSF1A/TNFR1 and mediates programmed cell death signaling and NF-kappaB activation. This protein reduces recruitment of inhibitor-of-apoptosis proteins (IAPs) by TRAF2 [48]. |
| TRAF3 | TNF receptor-associated factor 3 | +2.43 | Adapter protein and signal transducer that links members of the tumor necrosis factor receptor family to signaling pathways. Involved in the activation of NF-kappa-B and JNK and in apoptosis [49]. |
| BAG4 | BCL2-associated athanogene 4 | -2.46 | Member of the BAG1 anti-apoptotic protein family [31,32]. |
| XIAP | baculoviral IAP repeat-containing protein 4 | -6.96 | Apoptotic suppressor through binding to tumor necrosis factor receptor-associated factors TRAF1 and TRAF2 [28,29]. |
| BFAR | bifunctional apoptosis regulator | -3.25 | Apoptosis regulator with bifunctional anti-apoptotic activity for apoptosis triggered by death-receptors and mitochondrial factors [50]. |
| BNIP2 | BCL2/adenovirus E1B 19kDa interacting protein 2 | -6.50 | Member of the BCL2/adenovirus E1B 19 kD-interacting protein family. Its specific function is unknown; however, it interacts with the E1B 19 kD protein which is responsible for the protection of virally-induced cell death, as well as E1B 19 kD-like sequences of BCL2, an apoptotic protector [51]. |
| BNIP3L | BCL2/adenovirus E1B19kDa interacting protein 3-like | -3.25 | Same as BNIP2. May also function as a tumor suppressor and inhibits apoptosis induced by BNIP3 [51,52]. |
| CARD8 | caspase recruitment domain family, member 8 | -3.73 | Postulated to be a component of the inflammasome, a protein complex that plays a role in the activation of proinflammatory caspases. Also, acts as an adaptor molecule negatively regulating NFKB activation, CASP1-dependent IL1B secretion, and apoptosis [53]. |
| CASP3 | caspase 3, apoptosis-related cysteine peptidase | -8.00 | Involved in the activation cascade of caspases responsible for apoptosis execution. An effector caspases, responsible for cleaving downstream substrates [36]. |
| CASP4 | caspase 4, apoptosis-related cysteine peptidase | -13.00 | An initiator caspase able to cleave and activate its own precursor protein, as well as caspase 1 precursor. |
| CRADD | CASP2 and RIPK1 domain containing adaptor with death domain | -3.03 | Apoptotic adaptor molecule specific for caspase-2 and FASL/TNF receptor-interacting protein RIP [54]. |
| LTBR | lymphotoxin beta receptor, TNFR superfamily member 3 | -2.83 | Receptor for the heterotrimeric lymphotoxin containing LTA, LTB, and TNFS14/LIGHT. Pro-apoptotic via TRAF3 and TRAF5 [55,56]. |
| TNFS8 | tumor necrosis factor (ligand) superfamily, member 8 | -3.73 | A cytokine that belongs to the tumor necrosis factor (TNF) ligand family and has been reported to induce cell proliferation [57]. |
| TP53BP2 | tumor protein p53 binding protein | -5.66 | Regulates apoptosis and cell growth through interactions with other p53 regulatory molecules. Inhibits the ability of APPBP1 to conjugate NEDD8 to CUL1 decreasing apoptosis induction by APPBP1. Impedes cell cycle progression at G2/M checkpoint [58,59]. |