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. 2019 Jul 12;27(7):849–858. doi: 10.3727/096504018X15447833065047

Table 1.

The Targets and Mechanism of Triptolide (TPL) in Human Non-Small Cell Lung Cancer (NSCLC)

Target Action Outcome Model Used Reference(s)
MAPKs p-JNK↓; p-ERK↑; p-P38↑ Apoptosis↑; proliferation↓; A549; A549/Taxol 22, 23
MKP-1↓ Reversing antimetastatic effect of PPARγ agonist rosiglitazone H441 24
ERK2↑; caspase 3 and 8↑ Apo2L/TRAIL-induced apoptosis sensitization A549; NCI-H358; Calu1; SkLu1 27
NF-κB p65 transactivation↓ TRAIL-induced apoptosis↑ A549 26
IKBα phosphorylation and degradation↓ NF-κB nuclear translocation↓ Incidence↓ H460; H460; PC3; FEN1 E160D mice; LLC-grafted mice 29
TRAIL-induced NF-κB transcriptional activity↓ Sensitive to TRAIL-induced apoptosis↑ A549; NCl-H1299 30
NF-κB↓; NF-κB-regulated drug-resistant gene expression↓ Reversal of the Taxol resistance A549; A549/Taxol 51
HA-CD44/RHAMM ERK↓; Akt↓; EGFR↓ Growth and survival↓ A549; H520; H1299; H1650; H1975; A549 xenograft in male nude mice 34
Potential EGFR antagonist Proliferation↓ Molecular dynamics simulation; H2347 35
miRNA 126 miRNAs↑; 101 miRNAs↓ Altering miRNA expression profile H358 43
miR-21↓; PTEN protein↑; caspase 3 and 9↑ Proliferation↓; apoptosis↑ PC-9 45, 46
FAK p130Cas↓; Src↓; less metastatic colonization compared to control mice Migration, invasion, and metastasis↓ H460; A549; H358; H358 xenograft in NOD SCID γ mice 43
PI3K/Akt p-Akt↓; p-GSK-3β↑; Bax↑; caspases↑; Bcl-2↓ Proliferation↓; S-phase arrest A549; A549/Taxol 23
p-Akt↓ Cytotoxicity H1299, H460 36
Tumor-related protein expression Dysregulation of tumor-related protein Apoptosis↑; G2/M phase arrest A549 (ITRAQ-based proteomics analysis) 52
Keap1/Nrf2 Nrf2 transcriptional activity↓ Chemoresistance to antitumor drugs↓ LLC; Nrf2-KD; 3LL and Nrf2-KD xenograft in C57BL/6 mice 53
Wnt Epigenetic modifications to histone H3; WIF1 Growth↓ A549; H460; H358; H1299; E160D mice; A549 and H460 xenograft in NOD SCID γ mice 55
WIF1 demethylation Apoptosis↑; migration↓ A549; H460 57

MAPKs, mitogen-activated protein kinases; JNK, c-Jun N-terminal kinase; ERK, extracellular signal-regulated kinase; MKP-1, kinase phosphatase-1; Apo2L/TRAIL, Apo2L/tumor necrosis factor-related apoptosis-inducing ligand; Akt, protein kinase B; LLC, the Lewis lung cancer; EGFR, epidermal growth factor receptor, PTEN, phosphatase and tensin homolog; FAK, focal adhesion kinase; MMP14, matrix metalloproteinase 14, iTRAQ, isobaric tags for relative and absolute quantitation; Nrf2, nuclear factor erythroid 2-related factor 2; WIF1, Wnt inhibitory factor 1; ↑, activation/upregulation; ↓, suppression/downregulation.