Drug Information

Drug (ID: DG00108) and It's Reported Resistant Information

• Name: Arsenic trioxide
• Synonyms: Arsenox; Arsentrioxide; Naonobin; Trisenox; Trixenox; Acide arsenieux [French]; Anhydride arsenieux [French]; Arseni trioxydum; Arsenic blanc [French]; Arsenic trioxide [JAN]; Arsenigen saure [German]; Arsenious Acid Anhydride; Arsenious trioxide; Arsenous oxide [ISO]; Oxyde Arsenieux; Arsenic trioxide [UN1561] [Poison]; Arsenic oxide (As2O3); Arsenic(III) trioxide; Oxyde Arsenieux [ISO-French]; Trisenox (TN); Arsenic trioxide (JP15/USAN); Arsenic(3+)
• Indication:
  In total 1 Indication(s)
  Mature B-cell lymphoma [ICD-11: 2A85]; Approved; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Acute lymphocytic leukemia [ICD-11: 2B33]; [2]
  Lung cancer [ICD-11: 2C25]; [3]
• Target: Inhibitor of nuclear factor kappa-B kinase beta (IKKB); IKKB_HUMAN; [1]
• Formula: As2O3
• IsoSMILES: [O-2].[O-2].[O-2].[As+3].[As+3]
• InChI: 1S/2As.3O/q2*+3;3*-2
• InChIKey: QTLQKAJBUDWPIB-UHFFFAOYSA-N
• PubChem CID: 14888
• TTD Drug ID: D07VIK
• VARIDT ID: DR00119
• DrugBank ID: DB01169

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

ICD-02: Benign/in-situ/malignant neoplasm

Chronic myeloid leukemia [ICD-11: 2A20]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [4]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Chronic myelogenous leukemia [ICD-11: 2A20.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 post-transcriptionally down-regulates tumor suppressor PDCD4. AMO-miR-21 sensitized leukemic k562 cells to ATO by inducing apoptosis partially due to its up-regulation of PDCD4 protein level.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Programmed cell death protein 4 (PDCD4) [4]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Chronic myelogenous leukemia [ICD-11: 2A20.3]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell growth; Inhibition; hsa05200
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR-21 post-transcriptionally down-regulates tumor suppressor PDCD4. AMO-miR-21 sensitized leukemic k562 cells to ATO by inducing apoptosis partially due to its up-regulation of PDCD4 protein level.

Acute myeloid leukemia [ICD-11: 2A60]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-204 [1]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: Cancer progression; Inhibition; hsa05200
• In Vitro Model: AML-5 cells; Peripheral blood; Homo sapiens (Human); CVCL_1620
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Baculoviral IAP repeat-containing protein 6 (BIRC6) [1]

• Molecule Alteration: Expression; Down-regulation
• Sensitive Disease: Acute myeloid leukemia [ICD-11: 2A60.0]
• Experimental Note: Identified from the Human Clinical Data
• Cell Pathway Regulation: BIRC6/p53-mediated apoptosis signaling pathway; Activation; hsa04210
• In Vitro Model: AML-5 cells; Peripheral blood; Homo sapiens (Human); CVCL_1620
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• Experiment for Molecule Alteration: Western blot analysis; RT-qPCR
• Experiment for Drug Resistance: CCK8 assay; Flow cytometry assay
• Mechanism Description: miR-204 decreases ATO chemoresistance in AML cells at least partially via promoting BIRC6/p53-mediated apoptosis.

Acute lymphocytic leukemia [ICD-11: 2B33]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [2]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: PDCD4 has been reported to be involved in growth, apoptosis, invasion and cell cycle etc. AMO-miR-21 significantly sensitizes HL60 and k562 cells to ATO by inducing apoptosis, and these effects of AMO-miR-21 may be partially due to its up-regulation of PDCD4.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Programmed cell death protein 4 (PDCD4) [2]

• Molecule Alteration: Expression; Down-regulation
• Resistant Disease: Leukemia [ICD-11: 2B33.6]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• In Vitro Model: HL60 cells; Peripheral blood; Homo sapiens (Human); CVCL_0002
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: PDCD4 has been reported to be involved in growth, apoptosis, invasion and cell cycle etc. AMO-miR-21 significantly sensitizes HL60 and k562 cells to ATO by inducing apoptosis, and these effects of AMO-miR-21 may be partially due to its up-regulation of PDCD4.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-153 [5]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Leukemia [ICD-11: 2B33.6]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• In Vitro Model: K562 cells; Blood; Homo sapiens (Human); CVCL_0004
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Forced expression of miR-153 only in k562 cells has no significant effects on cell growth and apoptosis. However, when cells were additionally treated with As2O3, significant greater apoptosis was observed in the miR-153 overexpressed group.

Liver cancer [ICD-11: 2C12]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-539 [6]

• Molecule Alteration: Expression; Up-regulation
• Sensitive Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: Huh-7 cells; Liver; Homo sapiens (Human); CVCL_0336
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: Hep3B cells; Liver; Homo sapiens (Human); CVCL_0326
• In Vitro Model: PLC/PRF/5 cells; Liver; Homo sapiens (Human); CVCL_0485
• In Vitro Model: Skhep1 cells; Liver; Homo sapiens (Human); CVCL_0525
• In Vivo Model: Nude mouse xenograft model; Mus musculus
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: MTT assay; Colony formation assay; Flow cytometry assay
• Mechanism Description: microRNA-539 suppresses tumor growth and tumorigenesis and overcomes arsenic trioxide resistance in hepatocellular carcinoma.

Lung cancer [ICD-11: 2C25]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-155 [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: RT-qPCR
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Heme oxygenase 1 (HMOX1) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

Key Molecule: Quinone reductase 1 (NQO1) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

Key Molecule: NFE2-related factor 2 (NRF2) [3]

• Molecule Alteration: Expression; Up-regulation
• Resistant Disease: Lung cancer [ICD-11: 2C25.5]
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Nrf2 signaling pathway; Activation; hsa05208
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Immunoblotting assay
• Experiment for Drug Resistance: MTT Assay
• Mechanism Description: miR155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. miR155 mediated ATO resistance by upregulating the Nrf2 signaling pathway, but downregulating cellular apoptosis in lung cancer cells.

References

• Ref 1: MicroRNA-204 Potentiates the Sensitivity of Acute Myeloid Leukemia Cells to Arsenic Trioxide. Oncol Res. 2019 Sep 23;27(9):1035-1042. doi: 10.3727/096504019X15528367532612. Epub 2019 Apr 8.
• Ref 2: miRNA-21 regulates arsenic-induced anti-leukemia activity in myelogenous cell lines. Med Oncol. 2011 Mar;28(1):211-8. doi: 10.1007/s12032-009-9413-7. Epub 2010 Feb 9.
• Ref 3: miR-155 mediates arsenic trioxide resistance by activating Nrf2 and suppressing apoptosis in lung cancer cells. Sci Rep. 2017 Sep 22;7(1):12155. doi: 10.1038/s41598-017-06061-x.
• Ref 4: Anti-miR-21 oligonucleotide sensitizes leukemic K562 cells to arsenic trioxide by inducing apoptosis. Cancer Sci. 2010 Apr;101(4):948-54. doi: 10.1111/j.1349-7006.2010.01489.x. Epub 2010 Jan 7.
• Ref 5: miR-153 sensitized the K562 cells to As2O3-induced apoptosis. Med Oncol. 2012 Mar;29(1):243-7. doi: 10.1007/s12032-010-9807-6. Epub 2011 Jan 26.
• Ref 6: microRNA-539 suppresses tumor growth and tumorigenesis and overcomes arsenic trioxide resistance in hepatocellular carcinoma. Life Sci. 2016 Dec 1;166:34-40. doi: 10.1016/j.lfs.2016.10.002. Epub 2016 Oct 4.