Table 2 The combination therapy by apigenin and other chemodrugs
From: Apigenin in cancer therapy: anti-cancer effects and mechanisms of action
Cotreatment partner | Tumor type | Cell lines (concentration) | Combination effects | Mechanisms | Citations |
|---|---|---|---|---|---|
IFNγ | Cervical cancer | HeLa and SiHa (10 μM) | Enhance the anticancer activity | Targeting cyclin-dependent kinase 1 | [114] |
Paclitaxel | Ovarian cancer | SKOV3 (40 μM) | Overcome taxol resistance | Downregulation of Axl and Tyro3 RTKs expression | [100] |
Cisplatin | Multiple tumor types | HeLa, A549, HCT 116, H1299, and MCF-7 (30 µM) | Enhances the cisplatin cytotoxic effect | Increased DNA damage in a p53-dependent manner | [116] |
Prostate cancer stem cells | PC3 and CSCs (15 μM) | Enhance anticancer effects | Suppressed PI3K/AKT activation and protein expression of NF-κB | [117] | |
Laryngeal carcinoma | Hep-2 (40 μM) | Enhance the sensitivity to cisplatin | Inhibition of GLUT-1 and p-AKT | [119] | |
Solid Ehrlich carcinoma | Swiss male albino mice, intraperitoneally (100Â mg/kg) | Enhanced anti-cancer effect | Increased Beclin-1, caspases 3, 9 and JNK activities and decreased Mcl-1 | [44] | |
5-Fluorouracil (5-FU) | Hepatocellular carcinoma | SK-Hep-1 and BEL-7402 (4 μM) | Enhanced anticancer activity | Inhibition of ROS-mediated drug resistance and decreased Bcl-2 expression and loss of ΔΨm | [120] |
Pancreatic cancer | BxPC-3 (13 μM) | Potentiate anti-proliferative effect | Decreased nuclear GSK-3β and NF-κB p65 | [121] | |
Doxorubicin and etoposide | Leukaemia | CCRF-CEM and Jurkat (10 μM) | Enhancing cell cytotoxicity | Increased DNA damage | [122] |
TRAIL | Non-small cell lung cancer | A549 and H1299 (20 μM) | Enhance anti-tumor activity | Upregulated DR4/DR5 expression in a p53-dependent manner | [26] |
Anaplastic thyroid carcinoma | 8505C and CAL62 (40 μM) | Potentiates synergistic cytotoxicity | Reduced Bcl-2 and inactivation of ERK | [125] | |
Prostate cancer | DU145 (20 μM) | Enhancing cell apoptosis | Targeting adenine nucleotide translocase-2 | [124] | |
ABT-263 | Colon cancer | HCT116 and DLD1 (20 µM) | Enhance cell apoptosis | Inhibition of AKT and ERK signaling and Mcl-1 and upregulation of Bim | [24] |
miR-433-5p knockdown | Glioma stem cell | CD133-positive GSCs (20 μM) | Enhance cell apoptosis | Changes in Bax/Bcl-2 ratio, increased cytochrome c level, Apaf-1 induction, and caspase-3 activation | [126] |
miR-138 | Neuroblastoma | SK-N-DZ and SK-N-BE2 (100 μM) | Enhance cell apoptosis inhibition of cell viability | Increased Bax/Bcl-2 ratio and caspase-3,8 | [127] |
4-Hydroxy-2-nonenal (4-HNE) | The rat adrenal pheochromocytoma | PC12 (20 μM) | Attenuate 4-HNE-mediated cell death | Restore 4-HNE-induced ER homeostasis through modulating of UPR, Nrf2-ARE and MAPK pathways | [128] |