Drug (ID: DG00297) and It's Reported Resistant Information
Name
Mitomycin
Synonyms
Mitomycin C; mitomycin C; 1950/7/7; Mutamycin; Ametycine; Mitocin-C; Ametycin; Mitomycin-C; Mytozytrex; Mitomycinum; Mytomycin; Mitozytrex; Mitomycinum C; Mitocin C; Mitomycins; Mitamycin; MMC; Mitosol; Mitomycyna C; 7-Amino-9alpha-methoxymitosane; NSC-26980; Mitomycyna C [Polish]; Mito-C; Mit-C; Mitomycin (TN); Mitomycinum [INN-Latin]; Mitomycine [INN-French]; Mitomicina [INN-Spanish]; NCI-C04706; RCRA waste number U010; NSC26980; NSC 26980; Mitomycine; CCRIS 414; UNII-50SG953SK6; HSDB 3239; C15H18N4O5; EINECS 200-008-6; Mitomycin C,; Ametycin; Mitomicina; Muamycin; Mitomycin C from Streptomyces caespitosus; Mitomycin C (JP15); Mitomycin C, Streptomyces caespitosus; Muamycin (TN); Mitomycin (USP/INN); Mitomycin [USAN:INN:BAN]; Mitomycin C, Streptomyces caespitosus, Carrier-Free
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Indication
In total 3 Indication(s)
Breast cancer [ICD-11: 2C60]
Approved
[1]
Malignant digestive organ neoplasm [ICD-11: 2C11]
Approved
[1]
Solid tumour/cancer [ICD-11: 2A00-2F9Z]
Approved
[1]
Structure
Drug Resistance Disease(s)
Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
Gastric cancer [ICD-11: 2B72]
[2]
Liver cancer [ICD-11: 2C12]
[3]
Target Human Deoxyribonucleic acid (hDNA) NOUNIPROTAC [1]
Click to Show/Hide the Molecular Information and External Link(s) of This Drug
Formula
C15H18N4O5
IsoSMILES
CC1=C(C(=O)C2=C(C1=O)N3C[C@H]4[C@@H]([C@@]3([C@@H]2COC(=O)N)OC)N4)N
InChI
1S/C15H18N4O5/c1-5-9(16)12(21)8-6(4-24-14(17)22)15(23-2)13-7(18-13)3-19(15)10(8)11(5)20/h6-7,13,18H,3-4,16H2,1-2H3,(H2,17,22)/t6-,7+,13+,15-/m1/s1
InChIKey
NWIBSHFKIJFRCO-WUDYKRTCSA-N
PubChem CID
5746
ChEBI ID
CHEBI:27504
TTD Drug ID
D0Y0GH
VARIDT ID
DR01212
DrugBank ID
DB00305
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
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Brain cancer [ICD-11: 2A00]
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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-34 [4]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Medulloblastoma [ICD-11: 2A00.10]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53 signaling pathway Activation hsa04115
In Vitro Model UW228 cells Brain Homo sapiens (Human) CVCL_8585
R262 cells Bone marrow Homo sapiens (Human) CVCL_VU83
R300 cells Bone marrow Homo sapiens (Human) CVCL_VU84
UW426 cells Bone marrow Homo sapiens (Human) CVCL_DH82
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTS assay
Mechanism Description The repression of MAGE-A by miR-34a results in increased expression of p53 thus lead to resistance.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Melanoma-associated antigen 12 (MAGEA12) [4]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Medulloblastoma [ICD-11: 2A00.10]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53 signaling pathway Activation hsa04115
In Vitro Model UW228 cells Brain Homo sapiens (Human) CVCL_8585
R262 cells Bone marrow Homo sapiens (Human) CVCL_VU83
R300 cells Bone marrow Homo sapiens (Human) CVCL_VU84
UW426 cells Bone marrow Homo sapiens (Human) CVCL_DH82
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay
Mechanism Description The repression of MAGE-A by miR-34a results in increased expression of p53 thus lead to resistance.
Key Molecule: Melanoma-associated antigen 2 (MAGEA2) [4]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Medulloblastoma [ICD-11: 2A00.10]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53 signaling pathway Activation hsa04115
In Vitro Model UW228 cells Brain Homo sapiens (Human) CVCL_8585
R262 cells Bone marrow Homo sapiens (Human) CVCL_VU83
R300 cells Bone marrow Homo sapiens (Human) CVCL_VU84
UW426 cells Bone marrow Homo sapiens (Human) CVCL_DH82
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay
Mechanism Description The repression of MAGE-A by miR-34a results in increased expression of p53 thus lead to resistance.
Key Molecule: Melanoma-associated antigen 3 (MAGEA3) [4]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Medulloblastoma [ICD-11: 2A00.10]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53 signaling pathway Activation hsa04115
In Vitro Model UW228 cells Brain Homo sapiens (Human) CVCL_8585
R262 cells Bone marrow Homo sapiens (Human) CVCL_VU83
R300 cells Bone marrow Homo sapiens (Human) CVCL_VU84
UW426 cells Bone marrow Homo sapiens (Human) CVCL_DH82
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay
Mechanism Description The repression of MAGE-A by miR-34a results in increased expression of p53 thus lead to resistance.
Key Molecule: Melanoma-associated antigen 6 (MAGEA6) [4]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Medulloblastoma [ICD-11: 2A00.10]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
p53 signaling pathway Activation hsa04115
In Vitro Model UW228 cells Brain Homo sapiens (Human) CVCL_8585
R262 cells Bone marrow Homo sapiens (Human) CVCL_VU83
R300 cells Bone marrow Homo sapiens (Human) CVCL_VU84
UW426 cells Bone marrow Homo sapiens (Human) CVCL_DH82
Experiment for
Molecule Alteration
Western blotting analysis
Experiment for
Drug Resistance
MTS assay
Mechanism Description The repression of MAGE-A by miR-34a results in increased expression of p53 thus lead to resistance.
Esophageal cancer [ICD-11: 2B70]
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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-223 [5]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Esophageal adenocarcinoma [ICD-11: 2B70.2]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
Cell viability Inhibition hsa05200
In Vitro Model OE33 cellss Esophagus Homo sapiens (Human) CVCL_0471
HEEpiC cells Esophagus Homo sapiens (Human) N.A.
JHesoAD1 cells Esophagus Homo sapiens (Human) CVCL_8098
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTS assay
Mechanism Description The DNA damage repair protein poly(ADP-ribose) polymerase 1 (PARP1) is a bona fide target of miR-223, miR-223 up-regulation is also associated with reduced PARP1 transcripts, and an increased sensitivity to cis-diamminedichloroplatinum (II) (Cisplatin), Doxorubicin and Mitomycin C.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Poly[ADP-ribose] synthase 1 (PARP1) [5]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Esophageal adenocarcinoma [ICD-11: 2B70.2]
Experimental Note Identified from the Human Clinical Data
Cell Pathway Regulation Cell migration Activation hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model OE33 cellss Esophagus Homo sapiens (Human) CVCL_0471
HEEpiC cells Esophagus Homo sapiens (Human) N.A.
JHesoAD1 cells Esophagus Homo sapiens (Human) CVCL_8098
Experiment for
Molecule Alteration
Luciferase reporter assay
Experiment for
Drug Resistance
MTS assay
Mechanism Description The DNA damage repair protein poly(ADP-ribose) polymerase 1 (PARP1) is a bona fide target of miR-223, miR-223 up-regulation is also associated with reduced PARP1 transcripts, and an increased sensitivity to cis-diamminedichloroplatinum (II) (Cisplatin), Doxorubicin and Mitomycin C.
Gastric cancer [ICD-11: 2B72]
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Drug Resistance Data Categorized by Their Corresponding Mechanisms
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Hypoxia-inducible factor 2-alpha (EPAS1) [2]
Molecule Alteration Expression
Up-regulation
Resistant Disease Gastric cancer [ICD-11: 2B72.1]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model BGC-823 cells Gastric Homo sapiens (Human) CVCL_3360
BEL-7402 cells Liver Homo sapiens (Human) CVCL_5492
HepG2 cells Liver Homo sapiens (Human) CVCL_0027
HEK293 cells Kidney Homo sapiens (Human) CVCL_0045
Experiment for
Molecule Alteration
Western blotting assay
Experiment for
Drug Resistance
Flow cytometry assay
Mechanism Description Over-expression of EPAS-1 increased the expression of PXR responsive genes, enhanced the proliferation of BGC-823 cells and boosted the resistance of BGC-823 cells against the cytotoxicity of chemotherapeutic drugs, e.g. Mitomycin C and Paclitaxel.EPAS-1 reduces BGC-823 cell apoptosis induced by Mitomycin C and Paclitaxel.
Drug Sensitivity Data Categorized by Their Corresponding Mechanisms
       Epigenetic Alteration of DNA, RNA or Protein (EADR) Click to Show/Hide
Key Molecule: hsa-mir-495 [1]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration
RT-qPCR
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Receptor tyrosine-protein kinase erbB-2 (ERBB2) [1]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Gastric cancer [ICD-11: 2B72.1]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation Cell apoptosis Activation hsa04210
Cell proliferation Inhibition hsa05200
mTOR signaling pathway Inhibition hsa04150
In Vitro Model SGC7901 cells Gastric Homo sapiens (Human) CVCL_0520
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay; Flow cytometry assay
Mechanism Description The miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2.
Liver cancer [ICD-11: 2C12]
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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-146a [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The HCC Huh-7 cell line was treated with adramycin (ADM), cisplatin (DDP), carboplatin (CBP), mitomycin C (MMC) or vincristine (VCR) at increasing concentrations to develop drug-resistant sublines. Among these 51 upregulated and downregulated miRNAs, 12 miRNAs were upregulated and 13 miRNAs were downregulated in Huh-7/VCR. Upregulation of miR-27b, miR-181a, miR-146b-5p, miR-181d and miR-146a expression was verified using real-time RT-PCR in the parental and the five drug-resistant cell lines.
Key Molecule: hsa-miR-146b-5p [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The HCC Huh-7 cell line was treated with adramycin (ADM), cisplatin (DDP), carboplatin (CBP), mitomycin C (MMC) or vincristine (VCR) at increasing concentrations to develop drug-resistant sublines. Among these 51 upregulated and downregulated miRNAs, 12 miRNAs were upregulated and 13 miRNAs were downregulated in Huh-7/VCR. Upregulation of miR-27b, miR-181a, miR-146b-5p, miR-181d and miR-146a expression was verified using real-time RT-PCR in the parental and the five drug-resistant cell lines.
Key Molecule: hsa-mir-181a [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The HCC Huh-7 cell line was treated with adramycin (ADM), cisplatin (DDP), carboplatin (CBP), mitomycin C (MMC) or vincristine (VCR) at increasing concentrations to develop drug-resistant sublines. Among these 51 upregulated and downregulated miRNAs, 12 miRNAs were upregulated and 13 miRNAs were downregulated in Huh-7/VCR. Upregulation of miR-27b, miR-181a, miR-146b-5p, miR-181d and miR-146a expression was verified using real-time RT-PCR in the parental and the five drug-resistant cell lines.
Key Molecule: hsa-mir-181d [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The HCC Huh-7 cell line was treated with adramycin (ADM), cisplatin (DDP), carboplatin (CBP), mitomycin C (MMC) or vincristine (VCR) at increasing concentrations to develop drug-resistant sublines. Among these 51 upregulated and downregulated miRNAs, 12 miRNAs were upregulated and 13 miRNAs were downregulated in Huh-7/VCR. Upregulation of miR-27b, miR-181a, miR-146b-5p, miR-181d and miR-146a expression was verified using real-time RT-PCR in the parental and the five drug-resistant cell lines.
Key Molecule: hsa-mir-27b [3]
Molecule Alteration Expression
Up-regulation
Resistant Disease Hepatocellular carcinoma [ICD-11: 2C12.2]
Experimental Note Revealed Based on the Cell Line Data
In Vitro Model HCC Huh-7 cells Liver Homo sapiens (Human) CVCL_0336
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description The HCC Huh-7 cell line was treated with adramycin (ADM), cisplatin (DDP), carboplatin (CBP), mitomycin C (MMC) or vincristine (VCR) at increasing concentrations to develop drug-resistant sublines. Among these 51 upregulated and downregulated miRNAs, 12 miRNAs were upregulated and 13 miRNAs were downregulated in Huh-7/VCR. Upregulation of miR-27b, miR-181a, miR-146b-5p, miR-181d and miR-146a expression was verified using real-time RT-PCR in the parental and the five drug-resistant cell lines.
Cervical cancer [ICD-11: 2C77]
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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-145 [6]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Cervical cancer [ICD-11: 2C77.0]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation p53 signaling pathway Activation hsa04115
In Vitro Model C33A cells Uterus Homo sapiens (Human) CVCL_1094
Experiment for
Molecule Alteration
RT-PCR; Northern blotting analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description p53 signalling pathway mediates the cytotoxic effects of chemotherapy, miR-145 augments p53-mediated cytotoxic effects.
Bladder cancer [ICD-11: 2C94]
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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-31 [7]
Molecule Alteration Expression
Up-regulation
Sensitive Disease Bladder urothelial carcinoma [ICD-11: 2C94.2]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Regulation hsa04010
Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
Experiment for
Molecule Alteration
qRT-PCR
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-31 expression brings about (+) sensitivity of UBC to MMC by suppressing ITGA5 and downstream pathways.
       Unusual Activation of Pro-survival Pathway (UAPP) Click to Show/Hide
Key Molecule: Integrin alpha-5 (ITGA5) [7]
Molecule Alteration Expression
Down-regulation
Sensitive Disease Bladder urothelial carcinoma [ICD-11: 2C94.2]
Experimental Note Revealed Based on the Cell Line Data
Cell Pathway Regulation AKT/ERK signaling pathway Regulation hsa04010
Cell apoptosis Activation hsa04210
Cell invasion Inhibition hsa05200
Cell migration Inhibition hsa04670
Cell proliferation Inhibition hsa05200
In Vitro Model 5637 cells Bladder Homo sapiens (Human) CVCL_0126
T24 cells Bladder Homo sapiens (Human) CVCL_0554
Experiment for
Molecule Alteration
Western blot analysis
Experiment for
Drug Resistance
MTT assay
Mechanism Description miR-31 expression brings about (+) sensitivity of UBC to MMC by suppressing ITGA5 and downstream pathways.
References
Ref 1 MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2). Med Sci Monit. 2018 Aug 27;24:5960-5972. doi: 10.12659/MSM.909458.
Ref 2 Cross-talk between EPAS-1/HIF-2Alpha and PXR signaling pathway regulates multi-drug resistance of stomach cancer cell .Int J Biochem Cell Biol. 2016 Mar;72:73-88. doi: 10.1016/j.biocel.2016.01.006. Epub 2016 Jan 16. 10.1016/j.biocel.2016.01.006
Ref 3 Differential miRNA expression profiles in hepatocellular carcinoma cells and drug-resistant sublines. Oncol Rep. 2013 Feb;29(2):555-62. doi: 10.3892/or.2012.2155. Epub 2012 Nov 28.
Ref 4 miR-34a confers chemosensitivity through modulation of MAGE-A and p53 in medulloblastoma. Neuro Oncol. 2011 Feb;13(2):165-75. doi: 10.1093/neuonc/noq179. Epub 2010 Dec 22.
Ref 5 MicroRNA 223 is upregulated in the multistep progression of Barrett's esophagus and modulates sensitivity to chemotherapy by targeting PARP1. Clin Cancer Res. 2013 Aug 1;19(15):4067-78. doi: 10.1158/1078-0432.CCR-13-0601. Epub 2013 Jun 11.
Ref 6 Glucocorticoid regulation of a novel HPV-E6-p53-miR-145 pathway modulates invasion and therapy resistance of cervical cancer cells. J Pathol. 2012 Oct;228(2):148-57. doi: 10.1002/path.3997. Epub 2012 Apr 18.
Ref 7 MicroRNA-31 functions as a tumor suppressor and increases sensitivity to mitomycin-C in urothelial bladder cancer by targeting integrin Alpha5. Oncotarget. 2016 May 10;7(19):27445-57. doi: 10.18632/oncotarget.8479.

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