Table 1.
Modulation of ErbB receptors, NF-κB and HH/GLI signaling pathways by polyphenols in cancer cells.
| Signaling Pathway | Treatment | In Vitro Model | In Vivo Model | Antitumoral Effects | Reference |
|---|---|---|---|---|---|
| ErbB receptors | CUR | MDA-MB-468 breast cancer cells (40 µM) | ↓ EGFR phosphorylation
↓ c-fos expression ↓ ERK, MKK4, JNK activity |
[32] | |
| MDA-MB-231 breast cancer cells (30–50 µM) | ↓ Cell proliferation
↓ EGFR, ERK1/2, Akt, MAPK phosphorylation |
[33,34] | |||
| Breast cancer cells (6–50 µM) | BALB-neuT transgenic mice (2 mg in 50 µL corn oil p.o. thrice weekly) | ↓ Tumor growth
↓ ERK1/2 activity ↑ Bax/Bcl-2 ratio ↑ PARP cleavage ↓ Tumor multiplicity |
[29] | ||
| Gastric cancer cells (1–100 µM) | ↓ Cell proliferation
↓ ErbB2, cyclin D1 expression ↓ PAK1 activity |
[35] | |||
| LNCaP, C4-2B prostate cancer cells (0–100 µM) | ↓ Cell proliferation
↓ EGFR, ErbB2 expression |
[36] | |||
| Pancreatic and lung cancer cells (0–50 µM) | ↓ Cell proliferation
↓ COX-2, EGFR, phospho- ERK1/2 expression |
[37] | |||
| HEY ovarian cancer cells (2.5–160 µM) | ↓ Bcl-2, Akt expression
↑ p38 activity |
[38] | |||
| ErbB receptors | EGCG | MCF-7 breast cancer cells (5–20 µM) | ↓ ErbB2, ErbB3 phosphorylation
↓ MAPK pathway |
[39] | |
| mammary tumor NF639 and SMF cells (0–80 µg/mL) | ↓ Cell proliferation
↓ ErbB2/neu phosphorylation ↓ NF-κB, MAPK pathways |
[40] | |||
| HNSCC (10 µg/mL), breast cancer cells (30 µg/mL) | ↓ Cell proliferation
↓ EGFR, STAT3, Akt, c-fos activity |
[41,42] | |||
| SW837 colon carcinoma cells (30 µg/mL) | ↓ EGFR, ErbB2 and ErbB3 cellular levels | [43] | |||
| RES | HepG2 liver cancer cells (50–300 µM) | ↓ Cell proliferation
↓ Cyclin D1, Akt, p38 kinase expression ↑ Phospho-ERK1/2 protein levels |
[47] | ||
| A431 epidermoid carcinoma cells (0–100 µM) | ↓ Cyclin D1, MEK1, ERK1/2 expression | [48] | |||
| HT-29 colon cancer cells (25 µM) | ↓ JACK-STAT pathway
↓ iNOS, COX-2 expression |
[49] | |||
| Quercetin | SKBR3 breast cancer cells (100–200 µM) | ↓ ErbB2 tyrosin kinase activity
↓ PI3K, Akt phosphorylation |
[50] | ||
| HepG2 liver cancer cells (50 µM) | ↓ ERK1/2, Akt phosphorylation
↓ NF-κB pathway |
[51] | |||
| A549 lung cancer cells (0–58 µM) | ↓ Cell proliferation
↓ Akt-1 activation ↑ ERK-MEK1/2 phosphorylation |
[52] | |||
| Apigenin | PC-3, LNCaP prostate cancer cells (5–40 µM) | ↓ Cell proliferation
↑ Proportion of cells in G0/G1–phase ↓ Rb, p38 kinase and c-fos phosphorylation |
[53] | ||
| HNSCC cells (6–100 µM) | ↓ Cell proliferation
↓ EGFR, ErbB2 phosphorylation |
[55] | |||
| NF-κB | EGCG | A431 epidermoid carcinoma cells (10–40 µg/mL) | ↓ Cell proliferation
↓ NF-κB/p65 nuclear translocation |
[57] | |
| Delphinidin | PC-3 prostate cancer cells (30–180 µM) | Athymic (nu/nu) nude mice bearing prostate cancer tumors (2 mg i.p. thrice weekly) | ↓ Tumor growth
↓ IκB kinase γ , IκB-α phosphorylation ↓ NF-κB DNA binding activity |
[58,59] | |
| HCT-116 colon cancer cells (30–240 µM) | ↓ Cell proliferation
↓ IκB-α phosphorylation ↓ NF-κB activation |
[60] | |||
| Anthocyanin | rats with esophagus tumor (3.8 μmol/g/day p.o.) | ↓ Tumor development
↓ NF-κB, COX-2 expression |
[61] | ||
| CAL-27 oral cancer cells (0–500 µg/mL) | ↓ Cell proliferation, metastasis
↓ NF-κB, MMPs expression ↓ MAPK pathway |
[62] | |||
| CA, CAPE | HepG2 liver cancer cells (CA 100 µg/mL; CAPE 5 µg/mL) | nude mice injected with HepG2 cells (CA + CAPE 5 mg/kg s.c thrice weekly; CA + CAPE 20 mg/kg/day p.o. for 5 weeks) | ↓ Tumor growth
↓ NF-κB, MMP-9 activity ↓ Liver metastasis |
[63] | |
| CUR | Cervical cancer cells (5–60 µM) | ↓ IκB-α phosphorylation
↓ NF-κB activation |
[64] | ||
| ICR mice (1–25 µM) | ↓ COX-2 expression
↓ NF-κB activation ↓ NF-κB nuclear translocation ↓ ERK1/2 activity |
[65] | |||
| NF-κB | RES | MCF-7 breast cancer cells (50–150 µM) | ↓ Cell proliferation
↓ NF-κB activation ↓ Bcl-2 expression |
[66] | |
| OCIM2, OCI/AML3 myeloid leukemia cells (5–75 µM) | ↓ Cell proliferation
↓ NF-κB activation ↑ PARP cleavage ↑ Proportion of cells in S-phase |
[67] | |||
| HH/GLI | CUR | medulloblastoma cancer cells (40 µM) | ↓ SHH, GLI1, PTCH1 expression
↑ Proportion of cells in G2/M-phase |
[68] | |
| EGCG | SW1353, CRL-7891 chondrosarcoma cells (0–4 µM) | ↓ Cell proliferation
↓ GLI1, PTCH1 expression |
[69] | ||
| pancreatic cancer stem cells (20–60 µM) | ↓ Cell proliferation, invasion
↓ SMO, PTCH1, PTCH2, GLI1, GLI2 expression |
[70] | |||
| Apigein, baicalein, CUR, RES EGCG, genistein, quercetin | Pancreatic cancer stem cells, prostate cancer cells (20–30 µM) | ↓ GLI1 expression | [71,72] |
Abbreviations: p.o., per os; i.p., intraperitoneally; i.t., intratumorally; i.v., intravenously; s.c., subcutaneously.