Drug Combination Details
| General Information of the Combination (ID: C31431) | |||||
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| Name | Arsenic trioxide NP Info | + | Bortezomib Drug Info | ||
| Structure |
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| Disease |
Mantle cell lymphoma
[ICD-11: 2A85]
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Investigative | [1] | ||
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Multiple myeloma
[ICD-11: 2A83]
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Investigative | [2] | |||
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Acute lymphoblastic leukemia
[ICD-11: 2B33]
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Investigative | [3] | |||
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Acute myeloid leukemia
[ICD-11: 2A60]
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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 | ||||||
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| α. Enhancing Drug Efficacy by This Combination | ||||||
| Achieving Therapeutic Synergy | Click to Show/Hide | |||||
| Experiment 1 Reporting the Effect of This Combination | [3] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | ABL | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BCR | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PRKCD | Molecule Info |
Pathway MAP
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| In-vitro Model | K-562 | CVCL_0004 | Chronic myelogenous leukemia | Homo sapiens | ||
| Experimental
Result(s) |
Arsenic trioxide and bortezomib interact synergistically to induce apoptosis in chronic myelogenous leukemia cells resistant to imatinib mesylate through Bcr/Abl dependent mechanisms. | |||||
| Experiment 2 Reporting the Effect of This Combination | [5] | |||||
| Molecule(s)
Regulation |
Up-regulation | Expression | ABL | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | AIFM1 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | JNK1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | LMNB1 | Molecule Info |
Pathway MAP
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| Up-regulation | Phosphorylation | p38 beta | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | PARP1 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | PRKCD | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | Cytochrome c release | ||||
| In-vitro Model | K-562 | CVCL_0004 | Chronic myelogenous leukemia | Homo sapiens | ||
| U-937 | CVCL_0007 | Adult acute monocytic leukemia | Homo sapiens | |||
| NB4 | CVCL_0005 | Acute promyelocytic leukemia | Homo sapiens | |||
| NB4-LR1 | CVCL_8811 | Acute promyelocytic leukemia | Homo sapiens | |||
| HL-60 | CVCL_0002 | Adult acute myeloid leukemia | Homo sapiens | |||
| Kasumi-1 | CVCL_0589 | Acute myeloid leukemia | Homo sapiens | |||
| Jurkat | CVCL_0065 | T acute lymphoblastic leukemia | Homo sapiens | |||
| Raji | CVCL_0511 | EBV-related Burkitt lymphoma | Homo sapiens | |||
| Namalwa | CVCL_0067 | EBV-related Burkitt lymphoma | Homo sapiens | |||
| SU-DHL-4 | CVCL_0539 | B-cell lymphoma | Homo sapiens | |||
| Experimental
Result(s) |
Arsenic trioxide and proteasome inhibitor bortezomib synergistically induce apoptosis in leukemic cell. | |||||
| Experiment 3 Reporting the Effect of This Combination | [6] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Up-regulation | ROS generation | ||||
| In-vitro Model | HL-60 | CVCL_0002 | Adult acute myeloid leukemia | Homo sapiens | ||
| Experimental
Result(s) |
Synergistic antiproliferative effect of arsenic trioxide combined with bortezomib in HL61 cell line and primary blasts from patients affected by myeloproliferative disorders. | |||||
| Experiment 4 Reporting the Effect of This Combination | [2] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | CASP8 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| In-vitro Model | RPMI-8226 | CVCL_0014 | Plasma cell myeloma | Homo sapiens | ||
| Experimental
Result(s) |
Bortezomib can enhance ATO actions to induce apoptosis in RPMI 8266 cells, with decrease in expression of bcl-2 and increase of caspase-3, caspase-8 and caspase-9 proteins. | |||||
| Experiment 5 Reporting the Effect of This Combination | [1] | |||||
| Molecule(s)
Regulation |
Down-regulation | Expression | BCL-2 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | BIRC3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Cleavage | CASP9 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | CCND1 | Molecule Info |
Pathway MAP
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| Down-regulation | Expression | IL6 | 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 | RELA | Molecule Info |
Pathway MAP
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| In-vitro Model | JeKo-1 | CVCL_1865 | Mantle cell lymphoma | Homo sapiens | ||
| SP-53 | CVCL_C122 | Mantle cell lymphoma | Homo sapiens | |||
| Mino | CVCL_1872 | Mantle cell lymphoma | Homo sapiens | |||
| REC-1 | CVCL_1884 | Mantle cell lymphoma | Homo sapiens | |||
| Experimental
Result(s) |
Synergistic anticancer effects of arsenic trioxide with bortezomib in mantle cell lymphoma. | |||||
| Experiment 6 Reporting the Effect of This Combination | [4] | |||||
| Molecule(s)
Regulation |
Up-regulation | Cleavage | CASP3 | Molecule Info |
Pathway MAP
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| Up-regulation | Expression | MAP1LC3A | Molecule Info |
Pathway MAP
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| Induction | Degradation | PRAM1 | Molecule Info | |||
| Induction | Degradation | SQSTM1 | Molecule Info |
Pathway MAP
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| Biological
Regulation |
Increase | ROS generation | ||||
| Increase | Unfold protein response | |||||
| In-vitro Model | NB4 | CVCL_0005 | Acute promyelocytic leukemia | Homo sapiens | ||
| HS-5 | CVCL_3720 | Healthy | Homo sapiens | |||
| In-vivo Model | APL cells (5 * 104 cells/mouse) were injected intravenously via the tail vein into genetically compatible FVB/N recipients, without conditioning with either radiation or chemotherapy. | |||||
| Experimental
Result(s) |
A synergistic effect on combining ATO and bortezomib in vitro was noted in both ATO-sensitive and ATO-resistant APL cell lines. The mechanism of this synergy involved downregulation of the nuclear factor-KappaB pathway, increase in unfolded protein response (UPR) and an increase in reactive oxygen species generation in the malignant cell. | |||||
