Drug Combination Details
| General Information of the Combination (ID: C00179) | |||||
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| Name | Curcumin NP Info | + | 5-fluorouracil Drug Info | ||
| Structure |
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| Disease |
Colon cancer
[ICD-11: 2B90]
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Phase 1 | [1] | ||
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Prostate cancer
[ICD-11: 2C82]
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Investigative | [2] | |||
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Oral cavity/oesophagus/stomach in situ carcinoma
[ICD-11: 2E60]
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Investigative | [3] | |||
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Breast cancer
[ICD-11: 2C60]
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Investigative | [4] | |||
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Colorectal cancer
[ICD-11: 2B91]
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Investigative | [5] | |||
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Stomach cancer
[ICD-11: 2B72]
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Investigative | [6] | |||
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Bladder cancer
[ICD-11: 2C94]
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Investigative | [7] | |||
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Hepatocellular carcinoma
[ICD-11: 2C12]
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Investigative | [8] | |||
| Click to Show/Hide the Whole Disease Information of This Combination | |||||
| 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 | [9] | |||||
| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BECN1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | mTOR | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | PRKAA1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | SQSTM1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | ULK1 | Molecule Info |
Pathway MAP
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| In-vitro Model | HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | ||
| HT-29 | CVCL_0320 | Colon adenocarcinoma | Homo sapiens | |||
| In-vivo Model | HCT116 cells (2*106) in 0.2 mL PBS or saline was injected into the right flank of male BALB/c-nu/nu mice mice to form xenograft tumors. | |||||
| Experimental
Result(s) |
Curcumin could significantly augment the cytotoxicity of 5-Fu to the tumorous cells. Pre-treatment with curcumin followed by 5-Fu may mediate autophagy turnover both in vitro and in vivo via AMPK/ULK1-dependent autophagy inhibition and AKT modulation, which may account for the increased susceptibility of the colon cancer cells/xenograft to the cytotoxicity of 5-Fu. | |||||
| Experiment 2 Reporting the Effect of This Combination | [8] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | COX-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | SMMC-7721 | CVCL_0534 | Hepatocellular carcinoma | Homo sapiens | ||
| In-vivo Model | 0.2 mL SMMC-7721 cell suspension (5*106 cells/mL) was injected subcutaneously into the right forelimb of female BALB/c nude mice. | |||||
| Experimental
Result(s) |
The molar ratio of 2:1 (CU:5-FU) combination group showed strong synergistic effect in SMMC-7721cells. The mechanism of the synergistic effect may be related to the inhibition of the expression of NF-kappaB (overall) and COX-2 protein. | |||||
| Experiment 3 Reporting the Effect of This Combination | [10] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | COX-2 | Molecule Info |
Pathway MAP
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| In-vitro Model | HT-29 | CVCL_0320 | Colon adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Combination of curcumin and 5-FU showed synergism at higher doses against the human colon cancer cell line HT-29. This synergism was associated with the decreased expression of COX-2 protein. | |||||
| Experiment 4 Reporting the Effect of This Combination | [11] | |||||
| Biological
Regulation |
Blockade | Blocade of cell cycle in G2/M phase | ||||
| In-vitro Model | AGS | CVCL_0139 | Gastric adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Combining curcumin with 5-FU significantly increased growth inhibition of AGS cells compared with either curcumin or 5-FU alone. | |||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [3] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | NFKBIA | Molecule Info |
Pathway MAP
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| In-vitro Model | Eca-109 | CVCL_6898 | Esophageal squamous cell carcinoma | Homo sapiens | ||
| EC9706 | CVCL_E307 | Esophageal squamous cell carcinoma | Homo sapiens | |||
| In-vivo Model | A cell suspension of 200 mL (4*106 EC9706 cells) was inoculated subcutaneously into the right flank of male athymic BALB/c nude mice. | |||||
| Experimental
Result(s) |
NF-kappaB signaling pathway was constitutively activated in the ESCC cell lines. Curcumin suppressed the activation of NF-kappaB via the inhibition of IkappaBalpha phosphorylation, and downregulated the expressions of Bcl-2 and CyclinD1 in ESCC cell lines. | |||||
| Experiment 2 Reporting the Effect of This Combination | [5] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BMI1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | EZH2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | microRNA 101 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | microRNA 141 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | microRNA 200b | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | microRNA 200c | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | microRNA 429 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MYC | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | RNF2 | Molecule Info | |||
| Down-regulation | Expression | SUZ12 | Molecule Info | |||
| In-vitro Model | HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | ||
| SW480 | CVCL_0546 | Colon adenocarcinoma | Homo sapiens | |||
| In-vivo Model | Xenograft tumors were generated by subcutaneous injection of 5*106 HCT116-5FUR cells in male athymic nude mice. | |||||
| Experimental
Result(s) |
Combined treatment with curcumin and 5-FU enhanced cellular apoptosis and inhibited proliferation in both parental and 5FUR cells, whereas 5-FU alone was ineffective in 5FUR cells. Curcumin suppressed EMT in 5FUR cells by downregulating BMI1, SUZ12 and EZH2 transcripts, key mediators of cancer stemness-related polycomb repressive complex subunits. | |||||
| Experiment 3 Reporting the Effect of This Combination | [2] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | CDKN1A | Molecule Info |
Pathway MAP
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| Down-regulation | Activity | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | ||
| DU145 | CVCL_0105 | Prostate carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin enhances cytotoxicity of 5-FU in prostate cancer cells by inducing p21(WAF1/CIP1) and C/EBPbeta expressions and suppressing NF-kappaB activation. | |||||
| Experiment 4 Reporting the Effect of This Combination | [6] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | COX-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | MKN45 | CVCL_0434 | Gastric adenocarcinoma | Homo sapiens | ||
| AGS | CVCL_0139 | Gastric adenocarcinoma | Homo sapiens | |||
| In-vivo Model | Human gastric cancer MKN45 tumor xenografts were established in nude mice from cultured MKN45 cells by inoculating subcutaneously 0.2 mL of cell suspension (1.0*108 cells/mL) in the right flank of SPF grade female athymic nude mice. | |||||
| Experimental
Result(s) |
Curcumin enhances the anticancer effect of 5-FU against gastric cancer in vitro and in vivo. The possible molecular mechanism may be, at least in part, related to down-regulation of COX-2 and NF-kappaB pathways. | |||||
| Experiment 5 Reporting the Effect of This Combination | [7] | |||||
| In-vitro Model | Ej138 | CVCL_2443 | Bladder carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Combination of 5 uM curcumin with 5-FU significantly reduced its cytotoxicity in EJ138 cells, while 15 uM curcumin caused an opposite increase. | |||||
| β. Decreasing Adverse Drug Reaction by This Combination | ||||||
| Decreasing Adverse Drug Reaction | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [12] | |||||
| Molecule(s)
Regulation |
Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP7 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | TYMS | Molecule Info |
Pathway MAP
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| In-vitro Model | MCF-7 | CVCL_0031 | Invasive breast carcinoma | Homo sapiens | ||
| MDA-MB-231 | CVCL_0062 | Breast adenocarcinoma | Homo sapiens | |||
| SK-BR-3 | CVCL_0033 | Breast adenocarcinoma | Homo sapiens | |||
| T-47D | CVCL_0553 | Invasive breast carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin was found to sensitize the breast cancer cells to 5-FU through TS-dependent downregulation of nuclear factor-kappaB (NF-kappaB). | |||||
| Experiment 2 Reporting the Effect of This Combination | [4] | |||||
| In-vitro Model | MDA-MB-231 | CVCL_0062 | Breast adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
The addition of curcumin as an adjuvant therapy during 5-FU treatment enhance the chemotherapeutic effectiveness of 5-FU by protecting normal cells from reduced viability and thus permitting higher dosing or longer treatment times. | |||||
| γ. Reversing Drug Resistance by This Combination | ||||||
| Reversing Drug Resistance | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [13] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | ABCB1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | HSP20 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | Cell cycle arrest in G0/G1 phase | ||||
| In-vitro Model | HCT 8 | CVCL_2478 | Colon adenocarcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Down-regulation of P-gp and HSP-27, two multidrug resistance related factors, may be the mechanism of curcumin reversing the drug resistance of HCT-8/5-FU to 5-FU. | |||||
| Experiment 2 Reporting the Effect of This Combination | [14] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | NFKBIA | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| In-vitro Model | SGC-7901 | CVCL_0520 | Human gastric cancer | Homo sapiens | ||
| Experimental
Result(s) |
Curcumin can reverse 5-FU resistance and inhibits proliferation in GC cells by downregulating the NFkappaB-signaling pathway. | |||||
