Table 1.
Mechanism of action of kaempferol in cancer prevention. Up-arrow (↑) indicates up-regulation and down-arrow (↓) indicates down-regulation.
| Signaling Pathways |
Cancer | Cell Line | Mechanism | Effects | Ref. |
|---|---|---|---|---|---|
| Angiogenesis | Cervical cancer | OVCAR-3 and A2780/CP70 | VEGF gene expression and HIF-1alpha ↓ | VEGF gene expression at mRNA and protein levels was decreased by kaempferol. Kaempferol treatment decreased HIF-1alpha (regulator of VEGF) | [41] |
| OVCAR-3 and A2780/CP70 | VEGF secretion ↓ | Kaempferol inhibited VEGF secretion. Kaempferol decreased ERK phosphorylation, NFκB and cMyc expression | [31] | ||
| Apoptosis | Breast cancer | MB-453 | p53 ↑ | The kaempferol induced apoptosis and it was associated with the upregulation of p53 | [32] |
| Leukemia | MDA-MB-231 | Caspase 9, 3 and p-ATM ↑ | Kaempferol induced apoptosis and increased levels of γH2AX expression, cleaved caspase 9 and 3 | [47] | |
| HL-60 and NB4 | CASP3 and BAX/BCL-2 ratio ↑ | Expression of CASP3 and BAX/BCL-2 ratio increased and BCL-2 decreased | [43] | ||
| Tumor suppressor gene | Bladder cancer | EJ | PTEN↑ | Kaempferol enhanced PTEN expression. Kaempferol-induced apoptosis was partially attenuated in PTEN-knockdown cells | [33] |
| Autophagy | Liver cancer | SK-HEP-1 | AVO-positive cells, auto phagosomes, autophagic cell death ↑ | AMPK and AKT signaling pathways and CDK1/cyclin B expression contributed to kaempferol-induced death of autophagic cells and G2/M cell cycle arrest | [29] |
| Gastric cancer | AGS, NCI-N87, SNU-638 and MKN-74 | Autophagy and cell death ↑ | Kaempferol activates the IRE1-JNK-CHOP signaling from cytosol to nucleus, and G9a inhibition activates autophagic cell death in cancer cells | [48] | |
| hTERT pathways | Cervical cancer | HeLa | hTERT ↓ | Kaempferol induced cellular apoptosis and aging via downregulating hTERT pathways | [49] |
| Signal transducer and activator of transcription 3 (STAT3) | Ovarian cancer | OVACAR-3 | STAT3 ↓ | Kaempferol induced cell cycle arrest of cancer cells at the G2/M checkpoint and inhibited the MEK/ERK and STAT3 signal transduction pathways | [34] |
| Transcription factor AP-1 | Bone cancer | U-2 OS | DNA binding activity of AP-1 ↓ | Kaempferol reduced the AP-1DNA binding activity | [35] |
| Nuclear factor E2-related factor 2 (Nrf2) | Lung cancer | A549 and NCIH460 | Nrf2 mRNA and protein levels ↓ | Kaempferol is a powerful inhibitor of Nrf2 and can be used as a natural sensitizer and anti-cancer agent for lung cancer therapeutics | [50] |
| Phosphatidylinositol-3-kinase (PI3K)/AKT | Colorectal cancer | HCT-8 or HCT-116 | PI3K/Akt ↓ | Synergistic effect of kaempferol with 5-Fluorouracil was noticed in the inhibition of cell proliferation and induction of apoptosis via suppression of thymidylate synthase or attenuation of p-Akt activation | [51] |
| ERK/p38 pathway | Ovarian Cancer | OVCAR-3 and SKOV-3 | ERK1/2 and p38 ↑ | Kaempferol sensitized ovarian cancer cells to TRAIL-initiated apoptosis through enhancement of DR4 as well as DR5 via ERK/JNK/CHOP pathways | [52] |
| Wnt/β-catenin signaling | Retinal tumor | SO-RB50 | Wnt/β-catenin ↓ | Kaempferol caused G2/M arrest as well as apoptosis and also suppressed Wnt/β-catenin signaling via targeting ERRα | [53] |
| Cell cycle | Breast cancer | MDA-MB-231 | G1 phase ↓ Population of cells in the G2 phase ↑ |
After the treatment with kaempferol, the population of cells in the G1 phase was significantly reduced and the population of cells in the G2 phase was enhanced markedly | [54] |
| Liver cancer | 769-P and 786-O | Cells arrested at phase G2-M stage | After kaempferol treatment, most cells arrested chiefly at the phase G2-M stage | [37] | |
| K-HEP-1 | G2/M cell cycle arrest | Kaempferol treatment resulted in G2/M cell cycle arrest | [29] |