Table 4.
Some relevant examples involving the capacity of natural bioactive agents to regulate MAPK in parallel with another related pathway involved in cancer progression and invasion.
| Compounds | Disease | Preclinical Model | Molecular Target | Biological Relevance | Reference |
|---|---|---|---|---|---|
| Caffeic acid phenethyl ester (CAPE) + U0126 | Pancreatic ductal adenocarcinoma | MIAPaCa-2 and PANC-1 | ↓MAPK and NF-κB expression level |
Reduces cell growth by cell-type-specific activation of apoptosis (MIAPaCa-2 caspase-dependent and PANC-1 caspase-independent mode) | [136] |
| Apigenin | Choriocarcinoma | JAR and JEG3 | ↓PI3K/AKT and ERK1/2 expression level | Reduces cell viability and migratory capacity; increases apoptosis | [138] |
| Coumestrol | Prostate cancer | PC3 and LNCaP | ↑phosphorylation of ERK1/2, JNK, P90RSK, and P53; ↓phosphorylation of AKT proteins |
Inhibits cell proliferation and migration; activates apoptosis | [140] |
| Quercetin | Choriocarcinoma | JAR and JEG3 cells | ↓phosphorylation of AKT, P70S6K and S6; ↑phosphorylation of ERK1/2, P38, JNK and P90RSK proteins | Inhibition of proliferation, cell-cycle progression and invasion; stimulation of ROS production | [141] |
| Kaempferol | Endometrial malignant transformation | HUVECs andEBM-2 | ↓phosphorylation of ERK and p38; ERK, p38, Akt; ↓HIF-1α and VEGFR2 proteins |
Inhibits angiogenesis | [142] |
| Genistein | Melanoma | Murine melanoma cell line B16F10 | ↓ phosphorylation of FAK, paxillin, tensin-2, vinculin, p38, ERK, and JNK proteins |
Inhibits the growth and regulates the migration and invasion | [144] |
| Novasoy and genistein | Endometrial cancer | ECC-1 and RL-95-2 cells | ↑phosphorylation of p42/44 in both cell line; ↓ phosphorylation of S6 only in RL-95-2 cells |
Reduces cell proliferation and cell-cycle arrest in G2; induces apoptosis |
[143] |
| Resveratrol | T-cell acute lymphoblastic leukemia | T-ALL cell lines, Molt-4 (glucocorticoid resistant) and Jurkat (glucocorticoid resistant) | ↓Akt/mTOR/p70S6K/4E-BP1; ↑p38-MAPK |
Induces apoptosis and autophagy | [147] |
| Escine | Osteosarcoma | MNNG, Saos-2, MG-63, U-2OS | ↑ p38 expression level | Induces apoptosis and autophagy | [148] |
| Triterpenoids (21α-methylmelianodiol) | Lung cancer | A549 cells | ↓ ERK, p-ERK, JNK, p-JNK, p38, and no effect on p-p38 | Targets drug resistance via P-glycoprotein (P-gp)/MDR1-association | [149] |
| Toosendanin | Lung cancer | A549 and H1975 cells | ↓ phosphorylation of ERK; ↓Snail, TGFβ1 expression level | Inhibits TGFβ1-induced EMT and migration, invasion, and adhesion | [150] |
ROS: reactive oxygen species; JNKs: c-Jun N-terminal kinases; ERK: extracellular regulated MAP kinase; p38: p38 kinase; AKT: v-akt murine thymoma viral oncogene homolog 1; T-ALL: T-cell acute lymphoblastic leukemia; TGFβ: transforming growth factor beta; VEGFR: vascular endothelial growth factor; HIF: Hypoxia-inducible factors.