|
| Natural compound | Biological system/model | Doses | Main results | Ref |
|
| EGCG: in vitro experiments |
| Curcumin | TE-8 and SKGT-7 esophageal cancer cell lines | 20–40 μM EGCG
20–40 μM curcumin | Reduced viability and invasion ability, reduced pErk1/2 and COX-2, increased caspase-3 level | [161] |
| MDA-MB-231 breast cancer cell line | 25 μM EGCG
3 μM curcumin
| Increased synergistically the cytotoxicity correlated with G2/M phase arrest | [164] |
| MDA-MB-231 and MCF-7 breast cancer cell lines transfected with ErbB2 to mimic breast cancer stem cells | 10 μM EGCG
10 μM curcumin | Cotreatment reduced the number of CD44 positive cells, reduced the tumor-sphere formation, and reduced the level of pSTAT3 | [162] |
Resveratrol,
γ-tocotrienol | MCF-7 breast cancer cell line | 50 μM EGCG
25 μM resveratrol
10 μM γ-tocotrienol | Inhibited cell proliferation
Additive effect when EGCG was combined with γ-tocotrienol in reducing the levels of cyclin D1 and Bcl-2
Increased level of antioxidant enzyme NQO1 when all three phytochemicals were used | [159] |
| Genistein, quercetin | CWR22Rv1 prostate cancer cells | 2.5 μM EGCG
2.5 μM genistein
2.5 μM quercetin | Coadministration of EGCG with genistein or quercetin reduced the cell proliferation and increased cell death compared to each treatment alone (the effects were more pronounced in case of combination of EGCG with quercetin) | [160] |
| Luteolin | Several human head and neck cancer cells from the primary tumor and their lymph node metastasis (Tu212, Tu686, 686LN, and 886LN) and several lung cancer cell lines (H292, A549, H460, H358, H322, H1299, and Calu-1) | 30 μM EGCG
10 μM luteolin | Synergistically increased the level of apoptosis (3–5-fold) compared to the additive level
Mitochondrial translocation of p53 after the combined treatment | [158] |
|
| Curcumin: in vitro experiments |
| Resveratrol | Hepa 1–6 murine hepatocarcinoma cell line | 2.5–40 μM curcumin
10–160 μM luteolin (fixed ratio 1 : 4) | Synergistic effect of the cotreatment consisted in reduced cell survival. The following apoptosis effects were observed: increased annexin V-propidium iodide positive staining, increased caspase-3 activity, increased the number of the nuclei with apoptotic morphology, increased ROS production | [163] |
| Silymarin | DLD-1, LoVo, HCT116 human colon cancer cells | 0–100 μM curcumin
0–100 μM silymarin | Cotreatment induced: increased antiproliferative effects, increased apoptosis, reduced cell survival | [184] |
|
| EGCG: in vivo experiments |
| Curcumin | Xenograft nude mouse model with SKGT-4 esophageal cancer cells | 50 μg/kg EGCG
50 μg/kg curcumin | Reduced tumor size after cotreatment
Reduced expression of Ki67, pERK, and cyclooxygenase-2 in immunohistochemistry | [161] |
Xenograft nude mouse model with A549
non-small-cell lung cancer cells (females) | 100 mg/kg EGCG
20 mg/kg curcumin | Cotreatment protected the mice against weight loss, reduced the tumor growth, reduced cyclin D1 and B2, and reduced the level of the proliferation marker Ki-67 | [165] |
| Xenograft nude mouse model with MDA-MB-231 breast cancer cells (females) | 25 mg/kg EGCG
25 mg/kg curcumin | Cotreatment decreased the tumor volume (by 49%) and the protein expression level of VEGFR-1 (by 78%), but not the levels of EGFR and Akt | [164] |
| Luteolin | Xenograft nude mice with Tu212 hypopharyngeal cancer cell line | 125 mg/kg EGCG
10 mg/kg luteolin | Synergistically decreased in Ki-67 expression and increased in TUNEL positive cells and inhibition of tumor volume | [158] |
|
