Table 2.
Tannin derivatives as PARG inhibitor in cell culture models.
| Author | Cell system | Stressor | Compound | Effects |
|---|---|---|---|---|
| Tsai 1992 [56] | 34I cells (C3H mouse mammarian carcinoma) | Dexamethasone | Nobotanin B | PAR-degradation of HMG 14, 17 and histone H1 blocked, but not on HMG1 and HMG2; Glucocorticoid-regulated MMTV (=Mouse mammary tumor virus) mRNA synthesis ↓; Bioavailability: 0.3%. |
| Aoki 1995 [57] | 34I cells (C3H mouse mammarian carcinoma) | Dexamethasone | Nobotanin B/Oenothein B | Glucocorticoid-regulated MMTV mRNA synthesis ↓; Oenothein B → depoly(ADP-ribosylation of HMG 14 and 17 ↓ but not HMG 1, 2 and histone H1. |
| Ying 2000 [75] | Murine astro-cytes from ICR mice | H2O2 | Gallotannin | Preincubated dose-dependent cell death ↓ (24 and 72 h); No effect under parallel treatment with H2O2. |
| Ying 2001 [76] | Neurons from Swiss-Webster mice | H2O2 H2O2, MNNG, SIN-1, NMDA |
Nobotanin B/Gallotannin | Nobotanin B and gallotannin → H2O2- induced neuronal cell death (20-24 h) ↓; Nobotanin B and gallotannin → NMDA toxicity ↓; Glutamate toxicity ↓. |
| Astrocytes from Swiss- Webster mice | Cell death ↓; Prevents NAD+ drop (10 min); PAR-degradation (5, 10min) ↓; Negligible anti-oxidative effect. | |||
| Bakondi 2004 [77] | HaCaT (Human kera- tinocytes) | H2O2, ONOO- | Gallotannin | Cytotoxic; Caspase 3-activity (6 h) ↓; No effect on PAR accumulation; PAR-PARP-1 automodification ↓; NAD+ drop after 0.5, 1 and 2 h ↓. |
| Di Meglio 2004 [78] | Rat germinal cells | SIN-1, SNO | Gallotannin | DNA repair ↓. |
| Dumitriu 2004 [79] | PBMC (Human peripheral blood mono-nuclear cells) | UVB | Gallotannin | Inhibition of ABC transporters following irradiation ↓. |
| Falsig 2004 [67] | Primary astro- cytes (C57bl/6jbom mice) | H2O2, SIN-1 MNNG CCM (=TNFα, IL-1β, IFN-γ) |
Gallotannin | Cell death ↓; No effect on PAR. Cell death ↑ Gallotannin → nitrite formation from NO ↓; Gallotannin → iNOS ↑. |
| Keil 2004 [66] | HeLa (nuclear extracts) | Gallotannin | PAR levels in vitro (3 h) ↑; Degradation of PAR blocked. | |
| Rapizzi 2004 [80] | RAW 264.7 (Murine macro- phages) | MNNG, LPS, IFN-γ, H2O2 | Gallotannin | Per se iNOS ↑; COX-2 ↑; No induction of IL-1β and of TNFα; PAR accumulation (1 h) ↑ without any toxicity; No effect on basal NAD+ pool; NAD+ level stabilized after MNNG (1 h); No effect on AP-1, IRF-1 and pSTAT-1. |
| Uchiumi 2004 [74] | HL-60 (Human pro- myelocytic leu- kemia cells) | 12-O-tetradeca- noylphorbol-13- acetate | Gallotannin | Nuclear PARG activity (3 h) ↓ but not cyto- plasmic; Basal relative PARG expression ↓. |
| Erdelyi 2005 [81] | A549 (Human lung adenocar- cinoma epithelial cells) | TNFα, IL-1β | Gallotannin | 4 h after treatment: MCP-1 ↓; MIP-1β ↓; MCP-2 ↓; RANTES ↓; GCP-2 ↓; IL-6 ↓; ENA-78 ↓; fractalkine ↓; IL-1α ↓; IL-1β ↓; IL-8 ↓; CCR4 ↓; CCR5 ↓ by gallotannin, but not MIP-3α and CXCR4; Gallotannin per se induces IL-8; Binding of NF-κB to its consensus oligonucleotide ↓; NF-κB phosphorylation and nuclear translocation ↓; Gallotannin → basal and stress-induced AP-1 ↓; Gallotannin → pJNK ↑; p-p38 ↑; pATF2 ↑; pERK1/2 ↑; pCREB ↑; Protein phosphatases 1, 2A and PP1 ↓; No elevated PAR level. Gallotannin is in vitro a strong antioxidant. |
| Maruta 2007 [82] | Mid-S phase cell nuclei of HeLa cells | Oenothein B | DNA replication activity ↓. | |
| Formentini 2008 [58] | HeLa (Human cervical cancer cells) | MNNG | 3-galloyl-α,β-d-glucose | PAR degradation 15 and 30 min ↓; Cell death after 3 or 6 h ↓; AIF release ↓ (1 h, MNNG); No DNA strand break induction per se. |
| Tikoo 2010 [83] | H9c2 embryonic rat heart myoblasts | Doxorubicin | Gallotannin | Cell death ↓; Cytoplasmic vacuolization ↓; Bax ↓; Bcl-2 ↑; PARP-1 cleavage ↓. |
| MDA-MB-231 breast cancer cells | Toxicity of doxorubicin ↑; Gallotannin is toxic per se. |