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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 (100 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]