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Drug Combination Details

General Information of the Combination (ID: C16256)
Name Apigenin   NP Info  + 5-fluorouracil   Drug Info 
Structure +
Disease
Breast cancer [ICD-11: 2C60]
Investigative [1]
Hepatocellular carcinoma [ICD-11: 2C12]
Investigative [2]
Discovery agent [ICD-11: N.A.]
Investigative [3]
Colorectal cancer [ICD-11: 2B91]
Investigative [4]
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Combinatorial Therapeutic Effect(s) Validated Clinically or Experimentally
    α. Enhancing Drug Efficacy by This Combination
                 Achieving Therapeutic Synergy     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [2]
                    Molecule(s)
                    Regulation
Down-regulation Expression BCL-2  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage PARP1  Molecule Info 
Pathway MAP
                    Biological
                    Regulation
Up-regulation ROS generation
Down-regulation Loss of mitochondrial membrane potential
                    In-vitro Model SK-HEP-1 CVCL_0525 Hepatocellular carcinoma Homo sapiens
BEL-7402 CVCL_5492 Human hepatocellular carcinoma Homo sapiens
                    In-vivo Model SK-Hep-1 cells (5*106 cells per mice) were suspended in 100 L of serum-free RPMI-1640 medium, then subcutaneously injected into the left flank of nude mice (Male, 4-6 weeks old).
                    Experimental
                    Result(s)
Apigenin may potentiate the cytotoxicity of 5-FU in HCC via inhibition of ROS-mediated drug resistance and concurrent activation of the mitochondrial pathways of apoptosis.
                    Experiment 2 Reporting the Effect of This Combination [4]
                    Molecule(s)
                    Regulation
Up-regulation Phosphorylation PRKAA1  Molecule Info 
Pathway MAP
                    In-vitro Model HCT 15 CVCL_0292 Colon adenocarcinoma Homo sapiens
HT-29 CVCL_0320 Colon adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
The dual-drug liposomes demonstrated enhanced inhibition of angiogenesis, better reduction in cell proliferation and increased apoptotic potential. Cell signaling studies indicating a significant upregulation of pAMPK and activity against downstream targets by dual drug liposomes.
                 Augmenting Drug Sensitivity     Click to Show/Hide
                    Experiment 1 Reporting the Effect of This Combination [1]
                    Molecule(s)
                    Regulation
Down-regulation Expression AKT1  Molecule Info 
Pathway MAP
Down-regulation Expression HER2  Molecule Info 
Pathway MAP
                    In-vitro Model MDA-MB-453 CVCL_0418 Breast adenocarcinoma Homo sapiens
                    Experimental
                    Result(s)
5-fluorouracil acts synergistically with apigenin inhibiting cell growth and inducing apoptosis via the down-regulation of ErbB2 expression and Akt signaling.
                    Experiment 2 Reporting the Effect of This Combination [3]
                    Molecule(s)
                    Regulation
Up-regulation Expression BECN1  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP3  Molecule Info 
Pathway MAP
Up-regulation Cleavage CASP9  Molecule Info 
Pathway MAP
Down-regulation Expression GPX1  Molecule Info 
Pathway MAP
Up-regulation Expression JNK1  Molecule Info 
Pathway MAP
Down-regulation Expression MCL1  Molecule Info 
Pathway MAP
                    In-vivo Model 200 uL tumor cell suspensions, containing 2*106 Ehrlich ascites carcinoma cells, were subcutaneously injected into the right thigh of the hind limb of each mouse.
                    Experimental
                    Result(s)
The combination of 5-FU and apigenin had a greater effect than each of 5-FU or apigenin alone against solid Ehrlich carcinoma in mice.
References
Reference 1 5-Fluorouracil combined with apigenin enhances anticancer activity through induction of apoptosis in human breast cancer MDA-MB-453 cells. Oncol Rep. 2009 Dec;22(6):1533-7.
Reference 2 5-Fluorouracil combined with apigenin enhances anticancer activity through mitochondrial membrane potential mediated apoptosis in hepatocellular carcinoma. Clin Exp Pharmacol Physiol. 2015 Feb;42(2):146-53.
Reference 3 Apigenin potentiates the antitumor activity of 5-FU on solid Ehrlich carcinoma: Crosstalk between apoptotic and JNK-mediated autophagic cell death platforms. Toxicol Appl Pharmacol. 2017 Feb 1;316:27-35.
Reference 4 Dual drug loaded liposome bearing apigenin and 5-Fluorouracil for synergistic therapeutic efficacy in colorectal cancer. Colloids Surf B Biointerfaces. 2019 Aug 1;180:9-22.
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Cite NPCDR
Visitor Map
Correspondence

X. N. Sun, Y. T. Zhang, Y. Zhou, X. C. Lian, L. L. Yan, T. Pan, T. Jin, H. Xie, Z. M. Liang, W. Q. Qiu, J. X. Wang, Z. R. Li, F. Zhu*, X. B. Sui*. NPCDR: natural product-based drug combination and its disease-specific molecular regulation. Nucleic Acids Research. 50(D1): 1324-1333 (2020). PMID: 34664659

Prof. Feng ZHU  (zhufeng@zju.edu.cn)

College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China


Prof. Xinbing SUI  (hzzju@hznu.edu.cn)

School of Pharmacy and Department of Medical Oncology, the Affiliated Hospital of Hangzhou Normal University, Hangzhou Normal University, Hangzhou, China