Table 2.
In vitro and in vivo antitumoral effects of combinations of polyphenols.
| Treatment | In Vitro Model | In Vivo Model | Antitumoral Effects | Reference |
|---|---|---|---|---|
| Pterostilbene + quercetin (s) | B16M-F10 melanoma cells (40 µM pterostilbene + 20 µM quercetin) | C57BL/6J mice bearing B16M-F10 cells (20 mg/kg/day of each polyphenol i.v.) | ↓ Tumor growth
↓ Metastatic activity ↓ Bcl-2 expression ↑ Mice survival |
[105] |
| Thearubigin + genistein (s) | PC-3 prostate cancer cells (0.125–0.5 µg/mL thearubricin + 5–20 µg/mL genistein) | ↓ Cell proliferation
↑ Proportion of cells in G2/M-phase |
[106] | |
| Genistein + RES | SV40 rats bearing prostate cancer (83–250 mg/kg/day of each polyphenols p.o) | ↓ Tumor growth
↓ IGF-1 expression |
[107] | |
| Quercetin + EGCG (a) | PC-3, LNCaP prostate cancer cells (10–20 µM of each polyphenol) | SCID mice bearing LAPC-4 prostate cancer cells (0.2%–0.4% of each polyphenol/day p.o) | ↓ Tumor growth
↓ AR expression ↓ PI3K/Akt pathway ↑ Bax/Bcl-2 ratio |
[108,109] |
| CUR + EGCG (s) | A549, NCI-460NSCLC cells (10–20 µM of each polyphenol) | Lung cancer xenograft node mouse model (20 mg/kg/day of each polyphenol i.p.) | ↓ Tumor growth
↓ Cyclin D1 and B1 levels |
[110] |
| MDA-MB-231 breast cancer cells (2–3 µM CUR + 20–25 µM EGCG) | Athymic nude mice implanted with MDA-MB-231 cells (200 mg/kg/day CUR p.o. + 25 mg/kg/day EGCG i.p.) | ↓ Tumor volume
↑ Proportion of cells in G2/M-phase |
[111] | |
| Arc + CUR + EGCG (s) | LNCaP prostate cancer cells, MCF-7 breast cancer cells (1 μM Arc + 5–10 μM CUR + 40 μM EGCG) | ↓ Cell proliferation
↑ Proportion of cells inG0/G1-phase ↑ Bax/Bcl-2 ratio ↓ NF-κB, PI3K/Akt, STAT3 expression |
[112] | |
| Luteolin + EGCG (s) | HNSCC and lung cancer cells (10 μM luteolin + 30 μM EGCG) | Athymic nude mice implanted with HNSCC and lung cancer cells (125 mg/kg luteolin + 10 mg/kg EGCG p.o. 5 days a week) | ↓ Tumor growth
↑ PARP, caspase-3 cleavage ↑ p53 phosphorylation ↓ Ki-67 expression |
[113] |
| Ellagic acid + quercetin; Ellagic acid + RES; quercetin + RES (s) | MOLT-4 leukemia cells (ellagic acid + quercetin 0–40 μM; Ellagic acid + RES, quercetin + RES 0–140 mM) | ↓ Cell proliferation
↑ Caspase-3 activity |
[114,115] | |
| RES + CUR | NUB-7, LAN-5, IMR-32, SK-N-BE neuroblastoma cells (0–100 μM CUR + 0–200 μM RES) | ↓ Cell proliferation
↑ p53, Bax, p21 expression |
[116] | |
| SJ-RH4, RD/18 rhabdomyosarcoma cells, Saos-2 osteosarcoma cells (6–50 μM of each polyphenol) | ↓ Cell proliferation
↑ Bax/Bcl-2 ratio ↓ ERK phosphorylation |
[117] | ||
| CAL-27, SCC-15, FaDu, SALTO HNSCCcells (6–50 μM of each polyphenol) (a) | BALB/c mice implanted with SALTO cells (2 mg of each polyphenol in 50 μL of corn oil p.o. thrice weekly) | ↓ Tumor growth
↑ PARP cleavage ↑ Bax/Bcl-2 ratio ↓ ERK1/2 phosphorylation ↑ LC3 II expression |
[118] | |
| HCT-116 colon cancer cells (0–50 μM of each polyphenol) (s) | SCID mice implanted with HCT-116 cells (150 mg/kg/day RES + 500 mg/kg/day CUR p.o. for 3 weeks) | ↓ Tumor growth
↓ NF-κB, EGFR, IGF-1R activity |
[120] |
Abbreviations: (s), synergic effect; (a), additive effect; p.o., per os; i.p., intraperitoneally; i.t., intratumorally; i.v., intravenously; s.c., subcutaneously.