Table 4.
Overview on the interference of chromanols with molecular targets and key enzymes connecting inflammation and carcinogenesis.
| NF-кB | NLRP3 | MAPKs | Lipoxygenases | |||||
|---|---|---|---|---|---|---|---|---|
| α-TOH | ||||||||
| PMA NF-кB A BALB c/3T3 fibroblasts 50 µM no inhibition (Azzi et al., 1993) |
LPS NF-кB PE (Nucleus) RAW264.7 100 µM induction (Wallert et al., 2015) |
IL-1β, IL-6, TNF-α, LPS, PGE2, INF-γ h_DC NF-кB A 500 µM inhibition (Tan et al., 2005) |
IL-1β, IL-6, TNF-α, LPS, PGE2, INF-γ h_DC IкB-α Phos 500 µM inhibition (Tan et al., 2005) |
– 5-LO A enzyme 5 µM inhibition (Reddanna et al., 1985) |
– 5-LO A enzyme >1 µM inhibition (Pein et al., 2018) |
AA 5-LO PF PMNL 808 µM inhibition (Pein et al., 2018) |
||
| – p65 DNA BA MiaPaCa-2 50 µM no inhibition (Husain et al., 2011) |
AA 12-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||||||
| β-TOH | ||||||||
| PMA NF-кB A Balb c/3T3 fibroblasts 50 µM no inhibition (Azzi et al., 1993) |
– 5-LO A enzyme 750 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
|||||
| AA 5-LO PF PMNL 57 µM inhibition (Pein et al., 2018) |
||||||||
| γ-TOH | ||||||||
| TNF-α NF-кB Actv KBM-5 25 µM no inhibition (Ahn et al., 2007) |
– 5-LO A enzyme 2–3 µM inhibition (Reddanna et al., 1985) |
AA 5-LO PF PMNL 502 µM inhibition (Pein et al., 2018) |
– 5-LO A enzyme 910 nM inhibition (Pein et al., 2018) |
|||||
| – 5-LO A enzyme > 50 µM no inhibition (Jang et al., 2016) |
AA 12-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||||||
| – 5-LO A enzyme 200 µM inhibition (Jiang et al., 2011) |
||||||||
| δ-TOH | ||||||||
| – 5-LO A enzyme 310 nM inhibition (Pein et al., 2018) |
– 5-LO A enzyme > 50 µM no inhibition (Jang et al., 2016) |
|||||||
| AA 5-LO PF PMNL 85 µM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
||||||
| α-T3 | ||||||||
| – p65 DNA BA MiaPaCa-2 50 µM no inhibition (Husain et al., 2011) |
– p65 Trl MiaPaCa-2 50 µM no inhibition (Husain et al., 2011) |
– p65 Trl AsPC-1 50 µM no inhibition (Husain et al., 2011) |
– p65 Trl m_TT 50 µM no inhibition (Husain et al., 2011) |
– 5-LO A enzyme 330 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||
| AA 5-LO PF PMNL 277 µM inhibition (Pein et al., 2018) |
||||||||
| β-T3 | ||||||||
| – p65 DNA BA (Cytosol) MiaPaCa-2 50 µM inhibition (Husain et al., 2011) |
– p65 DNA BA (Nucleus) MiaPaCa-2 50 µM no inhibition (Husain et al., 2011) |
– p65 Trl MiaPaCa-2 50 µM inhibition (Husain et al., 2011) |
– p65 Trl m_TT 50 µM no inhibition (Husain et al., 2011) |
– 5-LO A enzyme 190 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||
| – p65 Trl AsPC-1 50 µM no inhibition (Husain et al., 2011) |
AA 5-LO PF PMNL 95 µM inhibition (Pein et al., 2018) |
|||||||
| γ-T3 | ||||||||
| – p65 Trl PC3 cells 40 µM inhibition (Yap et al., 2008) |
TNF-α NF-кB Actv RAW264.7 20 µM inhibition (Wang et al., 2015) |
TNF-α NF-кB Actv H1299, A293, MCF-7, U226, SCC4 25 µM inhibition (Ahn et al., 2007) |
diabetes IкB-α PE db/db mice 0.1% of diet induction (Kim et al., 2016) |
LPS/pal, Ng NLRP3 E m_BMDM 1 µM inhibition (Kim et al., 2016) |
diabetes p38 Phos db/db mice 0.1% of diet inhibition (Kim et al., 2016) |
- 5-LO A enzyme 200 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
| – NF-кB Actv mice 400 mg/kg/d inhibition (Kunnumakkara et al., 2010) |
– p65 DNA BA MiaPaCa-2 50 µM inhibition (Husain et al., 2011) |
– p65 Trl AsPC-1 50 µM inhibition (Husain et al., 2011) |
TNF-α IкB-α PE RAW264.7, m_BMDM 20 µM induction (Wang et al., 2015) |
diabetes NLRP3 E db/db mice derived PM/AT 0.1% of diet inhibition (Kim et al., 2016) |
diabetes ERK Phos db/db mice 0.1% of diet inhibition (Kim et al., 2016) |
AA 5-LO PF PMNL 132 µM inhibition (Pein et al., 2018) |
LPS/pal 5-LO GE BMDM 1 µM no inhibition (Kim et al., 2018) |
|
| – p65 Trl MiaPaCa-2 50 µM no inhibition (Husain et al., 2011) |
– p65 Trl m_TT 50 µM inhibition (Husain et al., 2011) |
TNF-α IкB-α Phos A549, PC3, MCF-7 20 µM inhibition (Wang et al., 2015) |
LPS/pal IкB-α PE m_BMDM 1 µM induction (Kim et al., 2018) |
TNF-α JNK Phos RAW264.7, m_BMDM 20 µM inhibition (Wang et al., 2015) |
||||
| – IкB-α Phos AsPC-1 50 µM inhibition (Husain et al., 2011) |
– IкB-α Phos MiaPaCa-2 50 µM inhibition (Husain et al., 2011) |
– IкB-α Phos m_TT 50 µM inhibition (Husain et al., 2011) |
LPS ERK Phos m_BMDM 0.5 µM inhibition (Kim et al., 2016) |
|||||
| δ-T3 | ||||||||
| – p65 DNA BA MiaPaCa-2 50 µM inhibition (Husain et al., 2011) |
– p65 Trl AsPC-1 50 µM inhibition (Husain et al., 2011) |
– p65 Trl MiaPaCa-1 50 µM inhibition (Husain et al., 2011) |
– IкB-α Phos MiaPaCa-2, 50 µM inhibition (Husain et al., 2011) |
– 5-LO A enzyme 170 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||
| – p65 Trl m_TT 50 µM inhibition (Husain et al., 2011) |
– IкB-α Phos MiaPaCa-2, 50 µM inhibition (Husain et al., 2011) |
– IкB-α Phos m_TT 50 µM inhibition (Husain et al., 2011) |
AA 5-LO PF PMNL 60 µM inhibition (Pein et al., 2018) |
|||||
| α-T-13′-OH | ||||||||
| – 5-LO A enzyme 350 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM induction (Pein et al., 2018) |
||||||
| AA 5-LO PF PMNL 190 nM inhibition (Pein et al., 2018) |
||||||||
| α-T-13′-COOH | ||||||||
| LPS p65 Trl RAW264.7 2.5 µM no inhibition (Wallert et al., 2015) |
– 5-LO A enzyme 270 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
|||||
| AA 5-LO PF PMNL 80 nM inhibition (Pein et al., 2018) |
||||||||
| δ-T-13′-OH | ||||||||
| – 5-LO A enzyme 120 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM induction (Pein et al., 2018) |
||||||
| AA 5-LO PF PMNL 540 nM inhibition (Pein et al., 2018) |
||||||||
| δ-T-13′-COOH | ||||||||
| – 5-LO A enzyme >1 µM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM induction (Pein et al., 2018) |
||||||
| AA 5-LO PF PMNL 2 µM inhibition (Pein et al., 2018) |
– 5-LO A enzyme 2 µM inhibition (Jang et al., 2016) |
Ca2+
5-LO PF HL-60 50 µM inhibition (Jiang et al., 2011) |
||||||
| – 5-LO A enzyme 0.5–1 µM inhibition (Jiang et al., 2011) |
||||||||
| α-T-5′-COOH | ||||||||
| – 5-LO A enzyme 750 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||||||
| α-T-3′-COOH | ||||||||
| – 5-LO A enzyme >3 µM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL 3 µM inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL 3 µM no inhibition (Pein et al., 2018) |
||||||
| δ-T3-13′-COOH | ||||||||
| – 5-LO A enzyme 35 nM inhibition (Pein et al., 2018) |
AA 12-LO PF PMNL > 3 µM no inhibition (Pein et al., 2018) |
AA 15-LO PF PMNL > 3 µM no inhibition (Pein et al., 2018) |
||||||
| AA 5-LO PF PMNL 260 nM inhibition (Pein et al., 2018) |
– 5-LO A enzyme 57 nM inhibition (Richomme et al., 2017) |
AA 5-LO PF PMNL 345 nM inhibition (Richomme et al., 2017) |
||||||
| – 5-LO A enzyme 1 µM inhibition (Jang et al., 2016) |
||||||||
| SCA D | ||||||||
| LPS p65 Phos RAW264.7 60 µM inhibition (Heo et al., 2014) |
LPS IкB-α Phos RAW264.7 60 µM inhibition (Heo et al., 2014) |
LPS JNK Phos RAW264.7 30 µM inhibition (Heo et al., 2014) |
||||||
| LPS ERK Phos RAW264.7 30 µM inhibition (Heo et al., 2014) |
||||||||
| SCA E | ||||||||
| LPS ERK Phos RAW264.7 58 µM inhibition (Lee et al., 2013) |
||||||||
| LPS p38 Phos RAW264.7 58 µM inhibition (Lee et al., 2013) |
||||||||
| LPS JNK Phos RAW264.7 58 µM inhibition (Lee et al., 2013) |
||||||||
| SCA G | ||||||||
| IL-1β p65/p50 Phos MG-63 40 µM inhibition (Yoon et al., 2012b) |
IL-1β IкB-α Phos MG-63 20 µM inhibition (Yoon et al., 2012b) |
IL-1β ERK Phos MG-63 40 µM inhibition (Yoon et al., 2012b) |
||||||
| IL-1β p38 Phos MG-63 20 µM inhibition (Yoon et al., 2012b) |
||||||||
| IL-1β JNK Phos MG-63 40 µM inhibition (Yoon et al., 2012b) |
||||||||
The content of each cell of the table is constructed as follows (read from top to bottom): (i) used stimulus; (ii) investigated parameter; (iii) cell type, tissue, mouse, or other models used for investigation; (iv) used concentration of the respective compound; (v) observed effect on the studied parameter; (vi) reference. In the publications where no stimulus was used or was required for the studies, the respective row is marked with “-”. Actv, activation; A, activity; AT, adipose tissue; BALB/c mice, albino laboratory-bred strain of the house mouse; AA, arachidonic acid; BA, binding affinity; BMDM, bone marrow derived macrophages; JNK, c-Jun N-terminal kinase; DC, dendritic cells; E, expression; ERK, extracellular-signal regulated kinase; 3T3, murine fibroblast cell line; GE, gene expression; h, human; MCF-7, human breast cancer cell line established by Michigan Cancer Foundation-7; SCC4, human head and neck squamous cell carcinoma cell line; HL-60, human leukemia cell line; H1299, human non-small cell lung carcinoma cell line; MiaPaCa-2, human pancreatic cancer cell line; AsPC-1, human pancreas adenocarcinoma cell line; U226, human peripheral blood myeloma, plasmacytoma cell line; MG-63, human osteosarcoma cell line; INF-γ, interferon γ; IL, interleukin; db/db mice, leptin receptor activity deficient mice; LPS, lipopolysaccharide; LO, lipoxygenase; RAW264.7, macrophages derived from abelson murine leukemia virus-induced tumor; MAPK, mitogen-activated protein kinase; m, murine; KBM-5, murine myelogenous leukemia cell line; Ng, nigericine; NLRP3, NLR family pyrin domain containing 3; NF-кB, nuclear factor kappa-light-chain-enhancer of activated B cells; p65, nuclear factor NF-кB p65 subunit; IкB, nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor; pal, palmitate; PM, peritoneal macrophages; PMA, phorbol-12-myristat-13-acetat; Phos, phosphorylation; PMNL, polymorphonuclear neutrophils; PF, product formation; PGE2, prostaglandin E2; PE, protein expression; Trl, translocation; TNF-α, tumor necrosis factor α; TT, tumor tissue.
All results obtained from in vivo studies are marked in gray.