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. 2019 Jun 19;24(12):2277. doi: 10.3390/molecules24122277

Table 1.

Studies of anticancer activities of kaempferol in vitro.

Cancer Types Mechanisms of Action Cancer Cells Lines Origin of Cells References
Bladder Downregulation: phosphorylated AKT (p-AKT), Cyclin D1, CDK4, Bid, Mcl-1 and Bcl-xL in human cells; DNMT3B expression in mouse cells
Upregulation: p38, p53, p21, p-BRCA1, p-ATM, Bid, Bax expression in human cells; DNA methylation in mouse cells
SV-HUC-1 (human), T24 and 5637 (mouse) Human, Mouse [100,124]
Blood Downregulation: p-ATM, phosphate-ataxia-telangiectasia, AKT, BCL2, ABCB1, and ABCC1 expression
Upregulation: CASP3 and BAX/BCL-2 expression, subG1 population, Rad3-related (p-ATR), 14-3-3 proteins sigma (14-3-3σ), DNA-dependent serine, MDC1 protein, p53 and p-H2AX expression
HL-60, NB4 Human [79,80]
Bone Downregulation: migration, MMP-2, MMP-9, and uPA expression, ERK, p38, and JNK phosphorylation and DNA binding activity of AP-1, endoplasmic reticulum stress and mitochondrial signaling pathways U-2 OS, HOB, 143B Human [109,110]
Brain Apoptosis Downregulation: phosphorylation of ERK, AKT, anti-apoptotic proteins XIAP and survivin expression, depolarization of mitochondrial membrane potential
Upregulation: caspase-3 activity
C6, A172 Rats, Human [55,57]
Breast Downregulation: Bcl2, E2, EMT-markers (N-cadherin, E-cadherin, Slug, and Snail), cathepsin D, cyclin D1, cyclin E, pAkt, pMEK1/2, pIRS-1, RhoA and Rac1 activation of ER/PR-silence and HER2-silence SK-BR-3
Upregulation: p21, bax γH2AX, cleaved caspase-3&-9, and p-ATM
Suppression of migration and invasion
Apoptosis, cell cycle arrest at G2/M and DNA damage, reduced cell migration and invasion ability
Triple-negative BC (TNBC) cell MDA-MB-231, MCF-7 Human [10,41,42,47,51,60]
Cervical Downregulation: PI3K/AKT and hTERT pathways
Upregulation: mitochondrial membrane potential disruption, intracellular free calcium elevation Apoptosis
HeLa, SiHa Human [111,112,114]
Colon Downregulation: CDK2, CDK4, cyclins D1, cyclin B1, cyclin E, cyclin A, Cdc25C, Cdc2, IGF-I&-II secretion, heregulin (HRG)-β expression and HRG-β-induced phosphorylation of the AKT, ERK-1/2, IGF-IR, and ErbB3
Upregulation: caspase-3,-8,-9, p21, p53, phospho-p38 MAPK and enhanced the PARP cleavages, JAK/STAT3, MAPK, PI3K/AKT, and NF-κB expression
Blocked ROS generation, cell cycle arrest at G1 and G2/M arrest, and cell migration
LS174, HCT15, HCT116, SW480, HT-29 Human [64,65,66,125]
Kidney Downregulation: MMP-2, AKT phosphorylation and FAK 786-O Human [97]
Liver Downregulation: mitochondrial membrane potential, mitochondrial swelling, SOCS3, STAT3, miR-21, PI3K/AKT/mTOR signaling pathway Upregulation: PTEN, caspase-3, JAK1, Tyk2, STAT1/2, endogenous IFN-α-regulated genes expression Hepatoma HepG2 Rat, Human [59,60,63]
Lung Downregulation: AKT/PI3K and ERK pathways, TIMP2, and MMP2 phosphorylation, Bcl-2, cyclin D1, claudin-2 expression
Inhibited STAT3 factor binding
Upregulation: PTEN, Bax, miR-340, Fas, cleaved-caspases 3, 8, and 9, and cleaved-PARP
Apoptosis, cell cycle arrest at G2/M, prevent migration and invasion
A549, HCCC9810, QBC939 Human, mice [90,92,94,96]
Oral Suppress migration and invasion
Downregulation: MMP-2, TIMP-2 mRNA, c-Jun activity, ERK1/2 phosphorylation
SCC4 Human [104]
Ovarian Upregulation: DR4, DR5, p53, p38, ERK1/2, CHOP, JNK, death receptors/FADD/Caspase-8 pathway Downregulation: anti-apoptotic proteins A2780/CP70, OVCAR-3, SKOV-3 Human [119,120,121]
Pancreatic Downregulation: EGFR-related AKT, Src, and ERK1/2, pathways
Upregulation: suppressive function of regulatory T cells (Tregs), FOXP3 expression
Block cell migration
Miapaca-2, Panc-1, SNU-213, Treg cells Human, Rats [76,77]
Prostate Downregulation: androgen receptor expression
Upregulation: caspase-8, -9, -3 and poly (ADP-ribose) polymerase proteins cleavage
C4-2, LNCaP Mice, Human [72,74]
Stomach Induce significant apoptosis and cell cycle arrest at G2/M
Downregulation: COX-2, Bcl-2 p-ERK, p-AKT expression
Upregulation: Bax, cleaved caspase-3 and -9
MKN28 and SGC7901 Human [116]