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Table 1 Effects of apigenin treatment alone on cancer cells

From: Apigenin in cancer therapy: anti-cancer effects and mechanisms of action

Tumor type

Cell lines (concentration)

Mice (dosages)

Therapeutic effects

Mechanisms

Citations

Colorectal cancer

SW480 (40 μM)

 

Inhibited proliferation, invasion and migration

Inhibited Wnt/β-catenin signaling

[11]

HCT116 (25 μM)

 

Inhibited proliferation; autophagy; apoptosis

Suppressed the expression of cyclin B1, Cdc2 and Cdc25c; induced PARP cleavage; induced LC3-II

[28]

DLD1 and SW480 (40 μM)

20 mg/kg (athymic nude mice, intraperitoneally)

Inhibited proliferation, invasion and migration

Attenuated NEDD9; reduced phosphorylations of FAK, Src, and Akt

[48]

SW480, DLD-1, and LS174T (40 μM)

50 mg/kg (BALB/c-nude mice, orthotopically implanted)

Inhibited proliferation, invasion and migration

Up-regulated TAGLN; down-regulated MMP-9 expression; decreasing phosphorylation of Akt

[50]

Breast cancer

BT-474 (40 μM)

 

Inhibited cell proliferation; apoptosis

Reduced the p-JAK1, p-JAK2 and p-STAT3; up-regulated the levels of cleaved caspase-8, cleaved caspase-3 and the cleavage of PARP

[25]

MDA-MD-231 (40 μM)

5, 25 mg/kg (BALB/c-nude mice, orthotopically injected)

Cell cycle arrest

Suppressed cyclin A, cyclin B, and CDK1; upregulated p21WAF1/CIP1; inhibited HDAC activity; induced histone H3 acetylation

[29]

MDA-MB-231 and T47D (40 μM)

 

Inhibited cell proliferation; apoptosis

Increased levels of caspase3, PARP cleavage and Bax/Bcl-2 ratios

[41]

MDA-MB-468 and 4T1 (30 μM)

 

Enhanced the immune responses

Inhibited IFN-γ-induced PD-L1 expression; inhibited STAT1

[58]

SKBR3 (40 μM)

 

Apoptosis

Reduced the expression of p-JAK2 and p-STAT3; inhibited VEGF

[98]

MDA-MB-453 (60 μM)

 

Inhibited cell proliferation; apoptosis

Up-regulated caspase-8, caspase-3 and the cleavage of PARP; inactivation of JAK2 and STAT3

[99]

Lung cancer

H1299 and H460 (20 μM)

 

Inhibited cell proliferation; apoptosis

Suppressed GLUT1

[13]

A549 (40 μM)

 

Inhibited cell proliferation, migration, invasion

Decreased the PI3K/Akt signaling pathway

[47]

Prostate cancer

LNCaP (20 μM)

 

Inhibited cell proliferation; apoptosis

Decreased cyclin D1, D2 and E; upregulated WAF1/p21

[15]

PC-3 and DU145 (20 μM)

20, 50 μg/mouse/day (athymic nude mice, oral gavage)

Cell cycle arret; apoptosis

Suppression of XIAP, c-IAP1, c-IAP2 and survivin; decreased Bcl-xL and Bcl-2 and increase in Bax protein

[22]

DU145 (20 μM)

 

Inhibited migration and invasion; cell cycle arrest

Increased E-cadherin; decreased snail and vimentin

[46]

 

20 and 50 μg/mouse/day (TRAMP mice, oral gavage)

Inhibited tumorigenesis

Inhibited IKK activation and restored the expression of IκBα

[89]

PC-3 and 22Rv1 (20 μM)

20 and 50 μg/mouse/day (athymic nude mice, oral gavage)

Inhibited cell proliferation, invasivion

Inactivation of IKKα; suppressed NF-ĸB/p65 activation

[90]

PC3-M and LNCaP C4-2B (25 μM)

 

Inhibited cell proliferation and metastases

Inhibited the Smad2/3 and Src/FAK/ Akt pathways

[110]

PC3 (25 μM)

 

Apoptosis; cell cycle arrest; suppressed stem cell migration

Increased p21 and p27; upregulated caspases-8, -3 and TNF-α; downregulation of PI3K/Akt and NF-κB signaling

[65]

Melanoma

A375, C8161 (40 μM)

 

Inhibited proliferation and invasion; apoptosis; cell cycle arrest

Activation of cleaved caspase-3 and cleaved PARP; decreased ERK1/2 proteins, p-AKT and p-mTOR

[14]

A2058, A375 (20 μM)

 

Inhibited metastasis

Inhibited the phosphorylation of FAK/ERK1/2

[82]

A375, G361 (20 μM)

 150 mg/kg (C57BL/6 mice, oral gavage)

Inhibited metastasis

Suppressed STAT3 phosphorylation; down-regulated MMP-2, MMP-9, VEGF and Twist1

[97]

Leukemia

HL60 (60 μM)

 

Apoptosis

Activation of caspase-9 and caspase-3

[23]

HL60 (50 μM); TF1 (30 μM)

 

Cell cycle arrest

Inhibited JAK/STAT pathway

[37]

U937 (40 μM)

20, 40 mg/kg (athymic nude mice, intraperitoneally)

Apoptosis

Inactivation of Akt; activation of JNK; downregulated Mcl-1 and Bcl-2

[112]

Ovarian cancer

A2780 (20, 40 μM)

5 mg/kg (BALB/c nude mice, intraperitoneally)

Inhibited adhesion, migration and invasion

Inhibited FAK expression

[49]

SKOV3 (20, 40 μM)

 

Inhibited the self-renewal capacity

Downregulated Gli1; inhibition of CK2α

[66]

Glioblastoma

GL-15 (50 μM)

 

Inhibited angiogenic

Reduced TGF-b1 production

[111]

U87MG and U373MG (25 μM)

 

Inhibited self-renewal capacity

Blocked the activation of c-Met signaling

[64]

Renal cell carcinoma

ACHN, 786-0, and Caki-1 (20 μM)

30 mg/kg (BALB/c-nude mice intraperitoneally)

Cell cycle arrest

p53 accumulation; modulated ATM signalling

[30]

Adenoid cystic carcinoma

ACC-2 (40 μM)

 

Inhibited proliferation; apoptosis

Suppressed the expression of GLUT-1

[31]

Papillary thyroid carcinoma

BCPAP (25 μM)

 

Cell cycle arrest; autophagy

Down-regulation of Cdc25C expression

[32]

Oral squamous cell carcinoma

SCC-25, HaCaT (100 μM)

 

Inhibited proliferation; apoptosis

Decreased expression of cyclin D-1 and E; inactivation of CDK1

[33]

Pancreatic cancer

 Murine Panc02 (20 μM)

25 mg/kg (female C57BL/6N mice, intraperitoneally)

Maintain T cell homeostasis

Stabilizing Ikaros expression

[60]

Mesothelioma

Malignant mesothelioma (MM) cells (50 μM)

20 mg/kg (C57BL/6 mice, oral gavage)

Apoptosis

Inhibited AKT and c-Jun phosphorylation, and inhibited NF-κB nuclear translocation

[91]

Osteosarcoma

U2OS and MG63 (50 μg/ml)

 

Inhibited proliferation and invasion

Inactivated Wnt/β-catenin signaling

[108]

Head and neck squamous cell carcinoma

HSC-3, HN-8, and HN- 30 (40 μM)

 

Suppressed cancer stem cell marker expression

Downregulated the stem cell markers of CD44,NANOG, and CD105, and abolished the hypoxia-induced increase

[63]

Cervical cancer

HeLa (40 μM)

 

Inhibited cell self-renewal capacity

Downregulation of CK2α expression

[67]