Drug Information

Drug (ID: DG00254) and It's Reported Resistant Information
Name
Mitoxantrone
Synonyms
DHAD; DHAQ; Dihydroxyanthraquinone; MIX; Misostol; Mitoxanthrone; Mitoxantron; Mitoxantrona; Mitoxantronum; Mitozantrone; DHAQ HCl; Mitoxantrone [INN]; Mitozantrone hydrochloride; Mitoxantrone 2HCl; Liposome Encapsulated Mitoxantrone (LEM); Misostol (TN); Mitoxantrona [INN-Spanish]; Mitoxantrone (INN); Mitoxantrone (free base); Mitoxantronum [INN-Latin]; Novantrone (TN); AN-584/42007670; Novantrone(R) (mitoxantrone for injection concentrate); DHAQ (*Diacetate salt*); MITOXANTRONE, Mitoxantrone Hydrochloride, Mitoxantrone dihydrochloride, MITOXANTHRONE HYDROCHLORIDE; MITOXANTRONE, 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)ANTHRA-9,10-QUINONE; 1,4-Bis(2-(2-hydroxyethylamino)ethyl)amino)-5,8-dihydroxyanthraquinone; 1,4-DIHYDROXY-5,8-BIS({2-[(2-HYDROXYETHYL)AMINO]ETHYL}AMINO)-9,10-ANTHRACENEDIONE; 1,4-Dihydroxy-5,8-bis(2-((2-hydroxyethyl)amino)ethylamino)-9,10-anthracenedione; 1,4-Dihydroxy-5,8-bis(5-hydroxy-3-azapentylamino)anthrachinon; 1,4-Dihydroxy-5,8-bis[2-(2-hydroxyethylamino)ethylamino]anthracene-9,10-dione; 1,4-Dihydroxy-5,8-bis[[2-[(2-hydroxyethyl)amino]ethyl]amino]-9,10-anthracenedione; 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthra-9,10-quinone; 1,4-dihydroxy-5,8-bis({2-[(2-hydroxyethyl)amino]ethyl}amino)anthracene-9,10-dione; 5,8-Bis((2-((2-hydroxyethyl)amino)ethyl)amino)-1,4-dihydroxyanthraquinone; 9,10-Anthracenedione, 1,4-dihydroxy-5,8-bis((2-((2-hydroxyethyl)amino)ethyl)amino)-(9CI)
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Indication
In total 2 Indication(s)
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Malignant haematopoietic neoplasm [ICD-11: 2B33]
Phase 1/2
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Clinically Reported Resistance for This Drug (1 diseases)
Keloid/hypertrophic scars [ICD-11: EE60]
[2]
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Breast cancer [ICD-11: 2C60]
[3]
Prostate cancer [ICD-11: 2C82]
[4]
Target DNA topoisomerase II (TOP2) TOP2A_HUMAN ;
TOP2B_HUMAN 		[1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C22H28N4O6
IsoSMILES
C1=CC(=C2C(=C1NCCNCCO)C(=O)C3=C(C=CC(=C3C2=O)O)O)NCCNCCO
InChI
1S/C22H28N4O6/c27-11-9-23-5-7-25-13-1-2-14(26-8-6-24-10-12-28)18-17(13)21(31)19-15(29)3-4-16(30)20(19)22(18)32/h1-4,23-30H,5-12H2
InChIKey
KKZJGLLVHKMTCM-UHFFFAOYSA-N
PubChem CID
4212
ChEBI ID
CHEBI:50729
TTD Drug ID
D0R3JB
VARIDT ID
DR00269
INTEDE ID
DR1102
DrugBank ID
DB01204
Type(s) of Resistant Mechanism of This Drug
  EADR: Epigenetic Alteration of DNA, RNA or Protein
  IDUE: Irregularity in Drug Uptake and Drug Efflux
Drug Resistance Data Categorized by Their Corresponding Diseases
ICD-02: Benign/in-situ/malignant neoplasm
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Solid tumour/cancer [ICD-11: 2A00-2F9Z]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [5]
Molecule Alteration Missense mutation
p.C592A
 Molecule Info 
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cytotoxicity assay
Mechanism Description Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [5]
Molecule Alteration Missense mutation
p.C592A+p.C603A
 Molecule Info 
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cytotoxicity assay
Mechanism Description Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [5]
Molecule Alteration Missense mutation
p.C603A+p.C608A
 Molecule Info 
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cytotoxicity assay
Mechanism Description Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [5]
Molecule Alteration Missense mutation
p.C608A
 Molecule Info 
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Cytotoxicity assay
Mechanism Description Cys-603 alone displayed mitoxantrone resistance close (although not identical) to the wt (-70%), whereas both Cys-608 alone and Cys-592 alone displayed an almost identical low resistance of -10 and 5% of the wt, respectively. For both C603A/C608A and C592A/C603A, we observed a marked decrease in resistance to mitoxantrone and a concomitant decrease in expr.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [6]
Molecule Alteration Missense mutation
p.K86M
 Molecule Info 
Sensitive Disease Solid tumour/cancer [ICD-11: 2A00-2F9Z]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 Colorimetric cytotoxicity assy assay
Mechanism Description Cells expressing ABCG2-wt or ABCG2-wt-MYC showed increased resistance to mitoxantrone as reflected in a sevenfold increase in IC50 value as compared to that observed for non-transfected cells (0.36 uM and 0.29 uM, for ABCG2-wt or ABCG2-wt-MYC expressing cells compared to 0.05 uM in non-transfected cells). ABCG2-k86M and ABCG2-k86M-HA displayed sensitivity comparable to that of non-transfected cells consistent with loss of function with IC50 values for mitoxantrone of 0.047 uM and and 0.043 uM
Chronic myeloid leukemia [ICD-11: 2A20]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [7]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Chronic myeloid leukemia [ICD-11: 2A20.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model K562/BCRP cells Blood Homo sapiens (Human) CVCL_0004
K562/MDR cells Blood Homo sapiens (Human) CVCL_0004
Experiment for
Drug Resistance		 Growth inhibition assay
Mechanism Description Some flavonoids have BCRP-inhibitory activity. 3',4',7-trimethoxyflavone showed the strongest anti-BCRP activity with RI50 values of 0.012 uM for SN-38 and 0.044 uM for mitoxantrone. 3',4',7-trimethoxyflavone and acacetin, showed only low anti-P-gp activity, with the remainder displaying no suppressive effects against P-gp. None of the flavonoids that we tested inhibite.
Acute myeloid leukemia [ICD-11: 2A60]
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Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-494 [1]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Acute myeloid leukemia [ICD-11: 2A60.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HL60 cells Peripheral blood Homo sapiens (Human) CVCL_0002
U937 cells Blood Homo sapiens (Human) CVCL_0007
KG1a cells Pleural effusion Homo sapiens (Human) CVCL_1824
In Vivo Model Mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay; Flow cytometry assay
Mechanism Description microRNA-494 activation suppresses bone marrow stromal cell-mediated drug resistance in acute myeloid leukemia cells.
Breast cancer [ICD-11: 2C60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-181a [8]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-181a down-regulated BCRP expression, and sensitized MX-resistant MCF-7/MX cells to MX.
Key Molecule: hsa-mir-328 [3]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MCF-7/MX100 cells Breast Homo sapiens (Human) CVCL_LB54
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 Sulforhodamine B assay
Mechanism Description miR-328 targets ABCG2 3'-UTR and, consequently, controls ABCG2 protein expression and influences drug disposition in human breast cancer cells. miR-328-directed down-regulation of ABCG2 expression in MCF-7/MX100 cells resulted in an increased mitoxantrone sensitivity.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [8]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-181a down-regulated BCRP expression, and sensitized MX-resistant MCF-7/MX cells to MX.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [8]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Activation hsa05200
Cell viability Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Overexpression of miR-181a down-regulated BCRP expression, and sensitized MX-resistant MCF-7/MX cells to MX.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [3]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MCF-7/MX100 cells Breast Homo sapiens (Human) CVCL_LB54
Experiment for
Molecule Alteration		 Immunoblotting analysis
Experiment for
Drug Resistance		 Sulforhodamine B assay
Mechanism Description miR-328 targets ABCG2 3'-UTR and, consequently, controls ABCG2 protein expression and influences drug disposition in human breast cancer cells. miR-328-directed down-regulation of ABCG2 expression in MCF-7/MX100 cells resulted in an increased mitoxantrone sensitivity.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [9]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
MCF-7/AdrVp cells Breast Homo sapiens (Human) CVCL_4Y46
MCF-7/AdrVpPR cells Breast Homo sapiens (Human) CVCL_4Y46
Experiment for
Molecule Alteration		 Northern blot analysis
Experiment for
Drug Resistance		 Flow cytometric assay
Mechanism Description The overexpression of BCRP mRNA in MCF-7/AdrVp cells, which is diminished in MCF-7/AdrVpPR, suggests an important role for BCRP in resistance to cytotoxic agents. Furthermore, the enforced overexpression of BCRP in MCF-7 cells diminished daunorubicin cellular accumulation and imparted a pattern of drug crossresistance to the transfected cells that was virtually identical to that of MCF-7/AdrVp.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-302a [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-302 inhibits BCRP expression via targeting the 3'-UTR of BCRP mRNA. miR-302 members may cooperatively downregulate BCRP expression to increase chemosensitivity of breast cancer cells. miR-302 gene cluster may be a potential target for reversing BCRP-mediated chemoresistance in breast cancer.
Key Molecule: hsa-mir-302b [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-302 inhibits BCRP expression via targeting the 3'-UTR of BCRP mRNA. miR-302 members may cooperatively downregulate BCRP expression to increase chemosensitivity of breast cancer cells. miR-302 gene cluster may be a potential target for reversing BCRP-mediated chemoresistance in breast cancer.
Key Molecule: hsa-mir-302c [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-302 inhibits BCRP expression via targeting the 3'-UTR of BCRP mRNA. miR-302 members may cooperatively downregulate BCRP expression to increase chemosensitivity of breast cancer cells. miR-302 gene cluster may be a potential target for reversing BCRP-mediated chemoresistance in breast cancer.
Key Molecule: hsa-mir-302d [10]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-302 inhibits BCRP expression via targeting the 3'-UTR of BCRP mRNA. miR-302 members may cooperatively downregulate BCRP expression to increase chemosensitivity of breast cancer cells. miR-302 gene cluster may be a potential target for reversing BCRP-mediated chemoresistance in breast cancer.
Key Molecule: hsa-mir-487a [11]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell survival Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 qRT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Ectopic miR-487a down-regulated BCRP expression at the mRNA and protein levels, increasing the intracellular accumulation and cytotoxicity of Mitoxantrone in resistant MCF-7/MX breast cancer cells.
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [10]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell proliferation Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model Nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blot analysis
Experiment for
Drug Resistance		 MTS assay
Mechanism Description miR-302 inhibits BCRP expression via targeting the 3'-UTR of BCRP mRNA. miR-302 members may cooperatively downregulate BCRP expression to increase chemosensitivity of breast cancer cells. miR-302 gene cluster may be a potential target for reversing BCRP-mediated chemoresistance in breast cancer.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [11]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell viability Inhibition hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Ectopic miR-487a down-regulated BCRP expression at the mRNA and protein levels, increasing the intracellular accumulation and cytotoxicity of Mitoxantrone in resistant MCF-7/MX breast cancer cells.
Key Molecule: ATP-binding cassette sub-family G2 (ABCG2) [11]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Sensitive Disease Breast cancer [ICD-11: 2C60.3]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
Cell survival Activation hsa05200
In Vitro Model MCF-7 cells Breast Homo sapiens (Human) CVCL_0031
In Vivo Model BALB/c nude mouse xenograft model Mus musculus
Experiment for
Molecule Alteration		 Western blotting analysis
Experiment for
Drug Resistance		 MTT assay
Mechanism Description Ectopic miR-487a down-regulated BCRP expression at the mRNA and protein levels, increasing the intracellular accumulation and cytotoxicity of Mitoxantrone in resistant MCF-7/MX breast cancer cells.
Prostate cancer [ICD-11: 2C82]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: Growth arrest specific 5 (GAS5) [4]
Molecule Alteration Expression
Down-regulation
 Molecule Info 
Resistant Disease Prostate cancer [ICD-11: 2C82.0]
 Disease Info 
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Inhibition hsa04210
In Vitro Model PC3 cells Prostate Homo sapiens (Human) CVCL_0035
22RV1 cells Prostate Homo sapiens (Human) CVCL_1045
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 Fluorescence microscopy test apoptosis assay
Mechanism Description Transient expression of GAS5 enhances apoptosis and decreases the survival of 22Rv1 cells, forced variation of GAS5 gene expression can modulate cellular responses to various apoptotic stimuli, including a range of chemotherapeutic drugs.
ICD-14: Skin diseases
Click to Show/Hide the Resistance Disease of This Class
Keloid/hypertrophic scars [ICD-11: EE60]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Irregularity in Drug Uptake and Drug Efflux (IDUE) Click to Show/Hide
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Keloid [ICD-11: EE60.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell growth Activation hsa05200
In Vitro Model Keloid fibroblasts N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.
Key Molecule: Multidrug resistance protein 1 (ABCB1) [2]
Molecule Alteration Expression
Up-regulation
 Molecule Info 
Resistant Disease Keloid [ICD-11: EE60.1]
 Disease Info 
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell growth Activation hsa05200
In Vitro Model Keloid fibroblasts N.A.
Experiment for
Molecule Alteration		 RT-PCR
Experiment for
Drug Resistance		 MTT assay
Mechanism Description MDR-1-positive keloid cells exhibited roundness as opposed to the usual spindle shape. Contrarily, MDR-1-positive cells in normal skin remained spindle shaped. Such a phenomenon suggests that MDR-1 positive keloid cells represent a subpopulation important in keloid pathogenesis. MDR-1 (also known as ABCB1 or P-glycoprotein) is one of the best characterized membrane transporters.
References
Ref 1 MicroRNA-494 Activation Suppresses Bone Marrow Stromal Cell-Mediated Drug Resistance in Acute Myeloid Leukemia Cells. J Cell Physiol. 2017 Jun;232(6):1387-1395. doi: 10.1002/jcp.25628. Epub 2016 Oct 19.
Ref 2 Enhanced expression of membrane transporter and drug resistance in keloid fibroblasts .Hum Pathol. 2012 Nov;43(11):2024-32. doi: 10.1016/j.humpath.2011.12.026. Epub 2012 May 21. 10.1016/j.humpath.2011.12.026
Ref 3 MicroRNA-328 negatively regulates the expression of breast cancer resistance protein (BCRP/ABCG2) in human cancer cells. Mol Pharmacol. 2009 Jun;75(6):1374-9. doi: 10.1124/mol.108.054163. Epub 2009 Mar 6.
Ref 4 Long non-coding RNA GAS5 regulates apoptosis in prostate cancer cell lines. Biochim Biophys Acta. 2013 Oct;1832(10):1613-23. doi: 10.1016/j.bbadis.2013.05.005. Epub 2013 May 12.
Ref 5 Identification of intra- and intermolecular disulfide bridges in the multidrug resistance transporter ABCG2. J Biol Chem. 2005 Nov 4;280(44):36926-34. doi: 10.1074/jbc.M502937200. Epub 2005 Aug 17.
Ref 6 Effect of Walker A mutation (K86M) on oligomerization and surface targeting of the multidrug resistance transporter ABCG2. J Cell Sci. 2005 Apr 1;118(Pt 7):1417-26. doi: 10.1242/jcs.01729. Epub 2005 Mar 15.
Ref 7 Flavonoids inhibit breast cancer resistance protein-mediated drug resistance: transporter specificity and structure-activity relationship. Cancer Chemother Pharmacol. 2007 Nov;60(6):789-97. doi: 10.1007/s00280-007-0426-7. Epub 2007 Mar 8.
Ref 8 MiR-181a enhances drug sensitivity in mitoxantone-resistant breast cancer cells by targeting breast cancer resistance protein (BCRP/ABCG2). Breast Cancer Res Treat. 2013 Jun;139(3):717-30. doi: 10.1007/s10549-013-2607-x. Epub 2013 Jun 19.
Ref 9 A multidrug resistance transporter from human MCF-7 breast cancer cells. Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15665-70. doi: 10.1073/pnas.95.26.15665.
Ref 10 miR-302a/b/c/d cooperatively inhibit BCRP expression to increase drug sensitivity in breast cancer cells. Gynecol Oncol. 2016 Jun;141(3):592-601. doi: 10.1016/j.ygyno.2015.11.034. Epub 2015 Nov 28.
Ref 11 MiR-487a resensitizes mitoxantrone (MX)-resistant breast cancer cells (MCF-7/MX) to MX by targeting breast cancer resistance protein (BCRP/ABCG2). Cancer Lett. 2013 Oct 1;339(1):107-15. doi: 10.1016/j.canlet.2013.07.016. Epub 2013 Jul 20.

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