Table 4.
Biological activities of flavonoids; ↑—induction, activation, upregulation, elevation; ↓—suppression, inactivation, downregulation, block.
| Cancer Type | Cell Line | Compound | Conc. | Main Biological Effects | Ref. |
|---|---|---|---|---|---|
| Skin cancer | A431, SCC-13 | Fisetin | 0–80 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↓ Cell viability ↓ Colony formation ↓ Δψm |
[88] |
| A375 | Luteolin | 0–80 µM | ↑ Apoptosis ↑ Cell cycle arrest at G0/G1 phase ↓ Colony formation ↓ Cell proliferation |
[89] | |
| B16F10 | Galangin | 0–100 µmol/L | ↑ Phosphor-p-38 MAPK ↑ Apoptosis ↓ Δψm ↓ Cell viability |
[90] | |
| SK-MEL-5, SK-MEL-28 | Silybin | 0–80 µM | ↑ Cell cycle arrest at G1 phase ↓ Cell viability ↓ Cell proliferation ↓ Kinase activity of MEK1/2 and RSK2 ↓ Expression of NF-κB, Ap-1 and STAT3 ↓ Phosphorylation of ERK1/2 and RSK2 |
[91] | |
| A375, RPMI-7951, Hs294T | Fisetin | 0–20 µM | ↓ Cell invasion ↓ Phosphorylation of MEK1/2 and ERK1/2 ↓ Activation of IKK ↓ Activation of the NF-κB signaling pathway |
[92] | |
| B16-F10 | Anthocyanins | 0–500 µg/mL | ↓ Cell proliferation | [93] | |
| 0–800 μg/mL | ↑ Cell cycle arrest at G0/G1 phase ↑ Apoptosis ↓ Cell viability ↓ Cell proliferation |
[94] | |||
| B16-F1 | Anthocyanins | 0–1 mg/mL | ↓ Cell growth ↓ Cell migration ↓ Tube formation ↓ Expression of MMP-2/-9 and VEGF ↓ Angiogenesis |
[95] | |
| A431 | Resveratrol + ALA-PDT therapy | 0–120 mg/mL | ↑ Apoptosis ↑ MAPK pathway ↓ Cell proliferation |
[96] | |
| A375.S2 | Chrysin | 0–15 µM | ↑ Cell morphological changes ↓ Cell viability ↓ Cell migration and invasion ↓ Expression of MMP-2 ↓ Expression of NF-κB p65 |
[97] | |
| Breast cancer | MDA-MB-231, MCF-7 | Luteolin | 0–100 µM | ↓ Cell viability ↓ Cell migration ↓ Expression of Notch-1, Hes-1, Hey, VEGF, Cyclin D1 and MMP -Regulating miRNAs |
[98] |
| MCF-7, MDA-MB-231 | Epigallocatechin-3-gallate | 0–40 µM | ↑ TIMP -3 levels↓ Cell proliferation by restoring the MP/TIMP balance |
[99] | |
| MCF-7 | Hesperetin | 0–200 µM | ↑ ROS generation ↑ ASK1/JNK pathway ↑ Apoptosis ↓ Δψm |
[87] | |
| BT-474 | Apigenin | 0–100 µM | ↑ Apoptosis ↓ STAT3 signaling ↓ Cell proliferation ↓ Chlorogenic survival |
[100] | |
| MCF-7 | Kaempferol | 0–100 µM | ↑ Extracellular lactate levels ↓ Cell proliferation ↓ Glucose uptake |
[101] | |
| 0–100 mg/mL | ↑ Apoptosis ↓ Cell proliferation ↓ Δψm |
[102] | |||
| MDA-MB-231 | Isorhamnetin | 0–40 µM | ↓ Cell proliferation ↓ Cell migration ↓ Cell adhesion ↓ Expression of MMP-2 and MMP-9 |
[103] | |
| MDA-MB-231, MDA-MB-468 | Quercetin | 0–100 µM | ↓ Cell proliferation ↓ Cell viability ↓ β-Catenin |
[104] | |
| MDA-MB-231 (4175) LM2, MDA-MB-435 | Luteolin | 0–100 µM | ↑ Apoptosis ↓ Cell migration ↓ Cell viability ↓ VEGF secretion |
[105] | |
| MDA-MB-231 | Luteolin | 0–40 µM | ↑ Apoptosis ↓ Cell viability ↓ Expression of MMP-9 ↓ Cell migration ↓ Cell invasion |
[106] | |
| MDA-MB-453, MCF-7 | Luteolin | 10 µM | ↑ Apoptosis ↑ Expression of miR-203 ↓ Cell viability ↓ Ras/Raf/MEK/ERK signaling pathways |
[107] | |
| MDA-MB-231, MCF-7, MDA-MB-453 | Delphinidin | 40 μmol/L | ↓ Cell viability ↓ Cell proliferation ↓ Cell migration ↓ Wnt/β-catenin signaling pathway -Modulating miR-34a and HOTAIR |
[108] | |
| MCF-7 | Quercetin | 25 μmol/mL | ↑ Apoptosis ↑ ROS levels and MDA ↓ Cell viability ↓ Cell proliferation ↓ Antioxidant enzymes activity |
[109] | |
| Ovarian cancer | ES2 | Delphinidin | 0–100 µM | ↑ Apoptosis ↓ Cell proliferation ↓ Cell migration ↓ AKT, ERK1/2, and MAPK signaling pathways |
[110] |
| SK-OV-3 | Genistein | 0–90 µM | ↑ Apoptosis ↓ Cell proliferation ↓ Δψm |
[111] | |
| OVCAR-3, SKOV-3 | Kaempferol | 0–100 µM | ↑ Apoptosis ↑ Expression of DR4, DR5, CHOP, JNK, ERK1/2, p38 ↓ Cell proliferation -Modulates the expression of apoptotic pathway proteins |
[112] | |
| CAOV3 | Quercetin | 0–100 µM | ↑ Apoptosis ↓ Cell viability |
[113] | |
| A2780/CP70, OVCAR-3 | Kaempferol | 0–50 µM | ↑ Cell cycle arrest at G2/M phase via Chk2 ↑ Apoptosis via death receptors ↓ Cell viability |
[114] | |
| PA-1 | Quercetin | 0–200 µM | ↑ Apoptosis ↓ Cell viability ↓ Bcl-2, Bcl-xL |
[115] | |
| A2780, OVCAR-3, SKOV-3 | Apigenin Luteolin Myricetin |
0–100 µM | ↑ ROS levels ↑ MDA levels ↑ Apoptosis ↑ Cell cycle arrest at G0/G1 and G2/M phase ↓ Cell viability |
[116] | |
| Cervical cancer | HeLa | Quercetin | 0–100 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↑ ROS levels ↓ Cell proliferation ↓ Δψm |
[117] |
| HeLa | Kaempferol | 0–100 mg/mL | ↓ Cell proliferation | [102] | |
| 2.5–100 µM | ↑ Bax ↓ Expression of Cyclin B1 ↓ Expression of CDK1 ↓ NF-κB nuclear translocation ↓ Bcl-2 |
[6] | |||
| 0–100 µM | ↑ Apoptosis ↓ Cell viability ↓ PI3K/AKT and hTERT pathways |
[118] | |||
| SiHa | Kaempferol | 0–100 µg/mL | ↑ Apoptosis ↑ Intracellular free Ca2+ ↓ Cell proliferation ↓ Δψm |
[119] | |
| Lung cancer | H446 | Genistein | 0–100 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↓ Cell proliferation ↓ Cell migration |
[120] |
| NCI-H1299, -H460 | Luteolin | 0–50 µM | ↑ Apoptosis ↓ Cell viability |
[121] | |
| A549 | Kaempferol | 0–50 µM | ↓ Cell proliferation ↓ Cell migration ↓ TGF-β1-induced EMT |
[122] | |
| 0–100 mg/mL | ↓ Cell proliferation | [102] | |||
| RAW 264.7 | Luteolin | 0–30 µM | ↓ Cell proliferation ↓ Cell migration ↓ STAT6 phosphorylation and the TAM phenotype ↓ Expression of CCL2 and migration of monocytes |
[123] | |
| A549 | Genistein | 0–200 µM | ↑ Apoptosis ↑ Bax mRNA level ↑ Expression of miR-27a ↓ Cell proliferation ↓ Cell viability ↓ Bcl-2 mRNA level ↓ Expression of MET protein |
[124,125] | |
| A549 | Apigenin | 0–100 µM | ↓ Cell proliferation ↓ Cell migration and invasion by targeting the PI3K/Akt signaling pathway |
[126] | |
| A549, H1299 | Daidzein | 0–80 µmol/L | ↑ Apoptosis ↓ Cell proliferation |
[41] | |
| A549 | Delphinidin | 0–80 µM | ↓ Cell proliferation ↓ ERK, mTOR and p70S6K signaling pathways |
[127] | |
| A549 | Kaempferol | 0–50 µM | ↑ Apoptosis ↑ Expression of miR-340 ↓ Cell proliferation ↓ Cell viability ↓ Expression of Cyclin D1 ↓ p-PI3K and p-AKT levels |
[128] | |
| A549 | Fisetin | 0–40 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↓ Cell viability ↓ Cell proliferation ↓ Cell adhesion ↓ Cell invasion ↓ Cell migration ↓ ERK signaling pathway via MEK1/2 |
[129] | |
| H1299, A549 | Epigallocatechin-3-gallate | 0–40 µM | ↑ Apoptosis ↓ Cell proliferation ↓ Expression of p-PI3K and p-Akt |
[130] | |
| A549 | Hesperetin | 0–100 µM | ↓ Cell proliferation | [9] | |
| A549 | Epigallocatechin-3 -gallate |
40 µM | ↑ miR-155 ↑ Cell cycle arrest at G0/G1 phase ↓ Cell proliferation ↓ miR-212 |
[131] | |
| Colon cancer | HT-29 | Kaempferol | 0–60 µmol/L | ↑ Apoptosis ↓ Δψm |
[132] |
| HT-29 | Epigallocatechin-3-gallate | 0–50 µM | ↑ MAPK and Akt signaling pathways ↓ p38 and ERK1/2 signaling pathways |
[133] | |
| HCT-116 | Resveratrol | 0–150 µM | ↑ Apoptosis ↑ DNA damage |
[134] | |
| HCT-116, SW480, LoVo, HT-29 | Naringenin | 0–200 µM | ↑ Apoptosis ↓ Cell viability |
[135] | |
| HCT-116, LoVo | Genistein | 0–100 µM | ↑ Apoptosis ↑ Bax mRNA level ↓ Cell proliferation ↓ Cell viability ↓ Phosphorylation of Akt |
[136] | |
| Liver cancer | HepG2, Huh-7, HA22T | Naringenin | 0–100 µM | ↓ Cell proliferation ↓ TPA-induced cancer cell proliferation |
[137] |
| Huh-7, HepG2, Hep3B, SK-Hep-1 | Xanthohumol | 0–15 µM | ↑ Apoptosis ↓ Cell viability ↓ Colony forming ↓ Notch1 signaling |
[138] | |
| HepG2 | Xanthohumol | 0–40 µM | ↓ cell proliferation ↑ Apoptosis -modulates NK-kB/p53 signaling pathways |
[139] | |
| Hepa1-6 | Genistein | 0–100 µM | ↑ Apoptosis ↓ Cell viability ↓ Cell proliferation |
[140] | |
| HepG2 | Kaempferol | 0–100 µM | ↑ Apoptosis ↓ Cell proliferation ↓ Cell migration ↓ Cell invasion ↓ Expression of miR-2I |
[141] | |
| Prostate cancer | PC-3 | Hesperetin | 0–120 µM | ↑ Apoptosis ↓ Cell proliferation ↓ NK-kB signaling pathway |
[142] |
| LNCaP | Kaempferol-3-O-rhamnoside | 0–926 µM | ↑ Apoptosis ↓ Cell proliferation |
[143] | |
| PC-3, DU145 | Resveratrol | 0–100 µM | ↑ Autophagy cell death | [144] | |
| Gastric cancer | SGC-7901, MKN28 | Kaempferol | 0–200 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↓ Cell proliferation ↓ Cell viability |
[145] |
| HGC-27, SGC-7901 | Apigenin | 0–20 µg/mL | ↑ Apoptosis ↓ Cell proliferation ↓ Δψm |
[146] | |
| SGC-7901, MGC-803, HGC-27 | Hesperetin | 0–400 µM | ↑ Apoptosis ↓ Cell proliferation ↓ Δψm ↓ Cell viability ↓ ROS levels |
[147] | |
| HGC-27, SGC-7901 | Myricetin | 0–40 µM | ↑ Apoptosis ↑ Cell cycle arrest at G2/M phase ↓ Cell proliferation |
[148] | |
| SCG-7901 | Kaempferol | 0–100 mg/mL | ↓ Cell proliferation | [102] |