Table 1.
Selected in vitro and in vivo studies on the therapeutic effects of apigenin in various cancers.
| Cancer | Dose (s) | Target gene | Model | Type of cell line | Effect (s) | References |
|---|---|---|---|---|---|---|
| Cervical cancer | 40 μM | CK2α | In vitro | HeLa | Inhibits cell self-renewal capacity | Liu et al., 2015a |
| Head and neck squamous cell carcinoma | 40 μM | CD44, NANOG, and CD105 | In vitro | HSC-3, HN-8, and HN- 30 | Inhibits the expression of cancer stem cell marker | Ketkaew et al., 2017 |
| Osteosarcoma | 50 μg/m | Wnt/β-catenin | In vitro | U2OS and MG63 | Inhibits proliferation and invasion | Liu et al., 2015b |
| Mesothelioma | 50 μM, 20 mg/kg | AKT and c-Jun phosphorylation/ NF-κB | In vitro, in vivo | Malignant mesothelioma (MM) cells | Induces Apoptosis | Masuelli et al., 2017 |
| Oral squamous cell carcinoma | 100 μM | cyclin D-1 and E | In vitro | SCC-25, HaCaT | Inhibits proliferation; Induces apoptosis | Maggioni et al., 2013 |
| Papillary thyroid carcinoma | 25 μM | Cdc25C | In vitro | BCPAP | Cell cycle arrest and autophagy induction | Zhang et al., 2015 |
| Adenoid cystic carcinoma | 40 μM | GLUT-1 | In vitro | ACC-2 | Inhibits proliferation; Induces apoptosis | Fang et al., 2015 |
| Renal cell carcinoma | 20 μM, 30 mg/kg | p53 | In vitro, in vivo | ACHN, 786-0, and Caki-1 | Induces cell cycle arrest | Meng et al., 2017 |
| Glioblastoma | 25 μM | c-Met | In vitro | U87MG and U373MG | Inhibits self-renewal capacity | Kim et al., 2016 |
| 50 μM | TGF-b1 | In vitro | GL-15 | Inhibits angiogenesis | Freitas et al., 2011 | |
| Ovarian cancer | 20,40 μM | FAK | In vitro | A2780 | Inhibits adhesion, migration, and invasion | Hu et al., 2008 |
| 20,40 μM | CK2α | In vitro | SKOV3 | Inhibits the self-renewal capacity | Tang et al., 2015 | |
| Leukemia | 60 μM | caspase-9 and caspase-3 | In vitro | HL60 | Induces apoptosis | Wang et al., 1999 |
| HL60 (50 μM) and TF1 (30 μM) | JAK/STAT | In vitro | HL60 / TF1 | Induces cell cycle arrest | Ruela-de-Sousa et al., 2010 | |
| 40 μM, 20, 40 mg/kg | Akt, JNK | In vitro, in vivo | U937 | Induces apoptosis | Budhraja et al., 2012 | |
| Melanoma | 40 μM | caspase-3/ PARP/ ERK1/2 proteins/ p-AKT and p-mTOR | In vitro | A375, C8161 | Inhibits proliferation and invasion; Induces apoptosis, and cell cycle arrest | Zhao et al., 2017a |
| 20 μM | FAK/ERK1/2 | In vitro | A2058, A375 | Inhibits metastasis | Hasnat et al., 2015 | |
| 20 μM, 150 mg/kg | MMP-2, MMP-9, VEGF, and Twist1 | In vitro, in vivo | A375, G361 | Inhibits metastasis | Cao et al., 2016 | |
| Prostate cancer | 20 μM | cyclin D1, D2, and E; WAF1/p21 | In vitro | LNCaP | Inhibits cell proliferation; Induces apoptosis | Gupta et al., 2002 |
| 20 μM, 20,50 μg/kg | XIAP, c-IAP1, c-IAP2/ Bcl-xL and Bcl-2 and Bax protein | In vitro, in vivo | PC-3 and DU145 | Induces cell cycle arrest and apoptosis | Shukla et al., 2014b | |
| 20 μM | E-cadherin/ snail and vimentin | In vitro | DU145 | Inhibited migration and invasion; cell cycle arrest | Zhu et al., 2015 | |
| 20 and 50 μg/kg | IKK – IκBα | In vivo | Inhibits tumorigenesis properties | Shukla et al., 2015b | ||
| 20 μM, 50 μg/ 50 μg/Kg | IKKα; NF-κB/p65 | In vitro, In vivo | PC-3 and 22Rv1 | Inhibits cell proliferation, invasion | Shukla et al., 2015a | |
| 25 μM | Smad2/3 and Src/FAK/Akt | In vitro | PC3-M and LNCaP C4-2B | Inhibits cell proliferation and metastases | Mirzoeva et al., 2014 | |
| 25 μM | p21 and p27; caspases-8,−3 and TNF-α; | In vitro | PC3 | Induces apoptosis and cell cycle arrest; suppresses stem cell migration | Erdogan et al., 2016 | |
| Lung cancer | 20 μM | GLUT 1 | In vitro | H1299 and H460 | Inhibits cell proliferation; Induces apoptosis | Lee et al., 2016 |
| 40 μM | PI3K/Akt | In vitro | A549 | Inhibits cell proliferation, migration, invasion | Zhu et al., 2017 | |
| Breast cancer | 40 μM | p-JAK1, p-JAK2 and p-STAT3; caspase-8, caspase-3; PARP | In vitro | BT-474 | Inhibits cell proliferation; Induces apoptosis | Seo et al., 2015a |
| 40 μM, 5, 25 mg/kg | cyclin A, cyclin B, and CDK1;p21WAF1/CIP1; | In vivo, In vitro | MDA-MD-231 | Induces cell cycle arrest | Tseng et al., 2017 | |
| 40 μM | caspase3, PARP and Bax/Bcl-2 | In vitro | MDA-MB-231 and T47D | Inhibits cell proliferation; Indices apoptosis | Cao et al., 2013 | |
| 30 μM | IFN-γ-; PD-L1; STAT1 | In vitro | MDA-MB-468 and 4T1 | Enhances the immune responses | Coombs et al., 2016 | |
| 40 μM | p-JAK2 and p- STAT3; VEGF | In vitro | SKBR3 | Induces apoptosis | Seo et al., 2015b | |
| 60 μM | caspase-8, caspase-3 and PARP; JAK2 and STAT3 | In vitro | MDA-MB-453 | Inhibits cell proliferation; Induces apoptosis | Seo et al., 2014 | |
| Colorectal cancer | 40 μM | Wnt/β-catenin | In vitro | SW480 | Inhibits proliferation, invasion and migration | Xu et al., 2016 |
| 25 μM | cyclin B1, Cdc2, and Cdc25c | In vitro | HCT116 | Inhibits proliferation; Induces autophagy and apoptosis | Lee et al., 2014 | |
| 40 μM, 20 mg/kg | NEDD9 | In vitro, in vivo | DLD1 and SW480 | Inhibits proliferation, invasion and migration | Dai et al., 2016 | |
| 40 μM, 50 mg/kg | TAGLN; MMP-9; Akt | In vitro, in vivo | SW480, DLD-1, and LS174T | Inhibits proliferation, invasion and migration | Chunhua et al., 2013 |