Drug Combination Details
| General Information of the Combination (ID: C62137) | |||||
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| Name | Curcumin NP Info | + | TNF-related apoptosis inducing ligand Drug Info | ||
| Structure |
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| Disease |
Prostate cancer
[ICD-11: 2C82]
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Investigative | [1] | ||
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Breast cancer
[ICD-11: 2C60]
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Investigative | [2] | |||
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Chronic myelogenous leukaemia
[ICD-11: 2A20]
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Investigative | [3] | |||
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Renal cell carcinoma
[ICD-11: 2C90]
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Investigative | [4] | |||
| 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 | ||||||
| Augmenting Drug Sensitivity | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [5] | |||||
| Molecule(s)
Regulation |
Down-regulation | Phosphorylation | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| In-vitro Model | LNCaP | CVCL_0395 | Prostate carcinoma | Homo sapiens | ||
| DU145 | CVCL_0105 | Prostate carcinoma | Homo sapiens | |||
| PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin sensitizes prostate cancer cells to TRAIL by inhibiting Akt-regulated NF-kappaB and NF-kappaB-dependent antiapoptotic Bcl-2, Bcl-xL, and XIAP. | |||||
| Experiment 2 Reporting the Effect of This Combination | [1] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | AKT1 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | p105 | Molecule Info |
Pathway MAP
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| In-vitro Model | PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Curcumin and TRAIL combination regimen is also the most effective treatment for inhibiting the growth of PC3 xenografts compared to curcumin or TRAIL monotherpy. The inhibition of PC3 tumors by combined treatment correlated with significant reduction in expression of p-Akt and NF-kappaB in tumor tissue. | |||||
| Experiment 3 Reporting the Effect of This Combination | [6] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | BAK | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BBC3 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BCL2L11 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BIRC5 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | ERK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PMAIP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | XIAP | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Induction | Loss of mitochondrial membrane potential | ||||
| In-vitro Model | LNCaP | CVCL_0395 | Prostate carcinoma | Homo sapiens | ||
| PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin enhanced the apoptosis-inducing potential of TRAIL in androgen-unresponsive PC-3 cells and sensitized androgen-responsive TRAIL-resistant LNCaP cells. | |||||
| Experiment 4 Reporting the Effect of This Combination | [7] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | BAK | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | BAX | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCL-xL | 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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| Up-regulation | Expression | CDKN1B | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | MMP-9 | Molecule Info |
Pathway MAP
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| Down-regulation | Activity | p105 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | PRAP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | VEGFA | Molecule Info |
Pathway MAP
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| In-vivo Model | LNCaP cells (2*106 cells as a 50% suspension in matrigel) in a final volume of 0.1 mL were injected subcutaneously at right flank of Balb c nude mice. | |||||
| Experimental
Result(s) |
Curcumin inhibited growth of LNCaP xenografts in nude mice by inducing apoptosis (TUNEL staining) and inhibiting proliferation (PCNA and Ki67 staining), and sensitized these tumors to undergo apoptosis by TRAIL via regulation of death receptors and members of Bcl-2 family and inactivation of NFkappaB. | |||||
| Experiment 5 Reporting the Effect of This Combination | [4] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CDK1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CFLAR | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | DDIT3 | Molecule Info |
Pathway MAP
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| Down-regulation | Phosphorylation | ERK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | ERK2 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | JNK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R1 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Induction | ROS generation | ||||
| In-vitro Model | ACHN | CVCL_1067 | Papillary renal cell carcinoma | Homo sapiens | ||
| Experimental
Result(s) |
Curcumin Sensitizes Kidney Cancer Cells to TRAIL-Induced Apoptosis via ROS Mediated Activation of JNK-CHOP Pathway and Upregulation of DR4. | |||||
| Experiment 6 Reporting the Effect of This Combination | [2] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BIRC3 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | ROS generation | ||||
| In-vitro Model | MCF-7 | CVCL_0031 | Invasive breast carcinoma | Homo sapiens | ||
| T-47D | CVCL_0553 | Invasive breast carcinoma | Homo sapiens | |||
| SK-BR-3 | CVCL_0033 | Breast adenocarcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin enhances TRAIL-induced apoptosis of breast cancer cells by regulating apoptosis-related proteins. | |||||
| Experiment 7 Reporting the Effect of This Combination | [8] | |||||
| Molecule(s)
Regulation |
Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | p105 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | DNA fragmentation | ||||
| Up-regulation | Annexin V binding | |||||
| Up-regulation | Release of cytochrome c from mitochondria | |||||
| Up-regulation | Truncation of proapoptotic Bid | |||||
| In-vitro Model | LNCaP | CVCL_0395 | Prostate carcinoma | Homo sapiens | ||
| DU145 | CVCL_0105 | Prostate carcinoma | Homo sapiens | |||
| PC-3 | CVCL_0035 | Prostate carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Combined curcumin and TRAIL treatment produced the most loss of viable cells by inducing apoptosis. | |||||
| Experiment 8 Reporting the Effect of This Combination | [9] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | TRAIL-R2 | Molecule Info |
Pathway MAP
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| In-vitro Model | Caki-1 | CVCL_0234 | Clear cell renal cell carcinoma | Homo sapiens | ||
| HCT 116 | CVCL_0291 | Colon carcinoma | Homo sapiens | |||
| HT-29 | CVCL_0320 | Colon adenocarcinoma | Homo sapiens | |||
| Hep-G2 | CVCL_0027 | Hepatocellular carcinoma | Homo sapiens | |||
| Hep 3B2.1-7 | CVCL_0326 | Childhood hepatocellular carcinoma | Homo sapiens | |||
| Experimental
Result(s) |
Curcumin sensitizes tumor necrosis factor-related apoptosis-inducing ligand (TRAIL)-induced apoptosis through reactive oxygen species-mediated upregulation of death receptor 5 (DR5). | |||||
| Experiment 9 Reporting the Effect of This Combination | [3] | |||||
| Biological
Regulation |
Induction | Cell cycle arrest in G2/M phase | ||||
| Modulation | DNA content | |||||
| In-vitro Model | KCL-22 | CVCL_2091 | Chronic myelogenous leukemia | Homo sapiens | ||
| Experimental
Result(s) |
Curcumin inhibits the cancer cell growth by inducing apoptosis and enhance the therapeutic potential of TRAIL. | |||||
