Drug Information

Drug (ID: DG00103) and It's Reported Resistant Information

• Name: Curcumin
• Synonyms: Curcumin; 458-37-7; Diferuloylmethane; Natural yellow 3; Turmeric yellow; Turmeric; Curcuma; Kacha haldi; Gelbwurz; Indian saffron; Curcumin I; Souchet; Halud; Halad; Haidr; Haldar; Merita earth; Yellow Ginger; Terra Merita; Yellow Root; Safran d'Inde; Yo-Kin; Golden seal; Curcuma oil; Orange Root; Oils, curcuma; CI Natural Yellow 3; Curcumine; Hydrastis; Indian turmeric; Yellow puccoon; Turmeric extract; Diferaloylmethane; Kurkumin [Czech]; (1E,6E)-1,7-Bis(4-hydroxy-3-methoxyphenyl)hepta-1,6-diene-3,5-dione; Tumeric yellow; Turmeric oil
• Indication:
  In total 1 Indication(s)
  Solid tumour/cancer [ICD-11: 2A00-2F9Z]; Phase 3; [1]
• Drug Resistance Disease(s):
  Disease(s) with Resistance Information Discovered by Cell Line Test for This Drug (2 diseases)
  Breast cancer [ICD-11: 2C60]; [1]
  Liver cancer [ICD-11: 2C12]; [2]
• Target: Albendazole monooxygenase (CYP3A4); CP3A4_HUMAN; [1]
• Target: Amyloid beta A4 protein (APP); A4_HUMAN; [1]
• Target: Carbonic anhydrase (CA); NOUNIPROTAC; [1]
• Target: Carbonic anhydrase I (CA-I); CAH1_HUMAN; [1]
• Target: Carbonic anhydrase II (CA-II); CAH2_HUMAN; [1]
• Target: Carbonic anhydrase IV (CA-IV); CAH4_HUMAN; [1]
• Target: Carbonic anhydrase IX (CA-IX); CAH9_HUMAN; [1]
• Target: Carbonic anhydrase VI (CA-VI); CAH6_HUMAN; [1]
• Target: Carbonic anhydrase XII (CA-XII); CAH12_HUMAN; [1]
• Target: Carbonic anhydrase XIV (CA-XIV); CAH14_HUMAN; [1]
• Target: DNA [cytosine-5]-methyltransferase (DNMT); NOUNIPROTAC; [1]
• Target: DNA [cytosine-5]-methyltransferase 3B (DNMT3B); DNM3B_HUMAN; [1]
• Target: Matrix metalloproteinase-13 (MMP-13); MMP13_HUMAN; [1]
• Target: Matrix metalloproteinase-9 (MMP-9); MMP9_HUMAN; [1]
• Target: Multidrug resistance protein (MDR); NOUNIPROTAC; [1]
• Target: Nitric-oxide synthase inducible (NOS2); NOS2_HUMAN; [1]
• Target: Prostaglandin G/H synthase 1 (COX-1); PGH1_HUMAN; [1]
• Target: Prostaglandin G/H synthase 2 (COX-2); PGH2_HUMAN; [1]
• Target: Xanthine dehydrogenase/oxidase (XDH); XDH_HUMAN; [1]
• Formula: C21H20O6
• IsoSMILES: COC1=C(C=CC(=C1)/C=C/C(=O)CC(=O)/C=C/C2=CC(=C(C=C2)O)OC)O
• InChI: 1S/C21H20O6/c1-26-20-11-14(5-9-18(20)24)3-7-16(22)13-17(23)8-4-15-6-10-19(25)21(12-15)27-2/h3-12,24-25H,13H2,1-2H3/b7-3+,8-4+
• InChIKey: VFLDPWHFBUODDF-FCXRPNKRSA-N
• PubChem CID: 969516
• ChEBI ID: CHEBI:3962
• TTD Drug ID: D07SDQ
• VARIDT ID: DR00559
• INTEDE ID: DR1941
• DrugBank ID: DB11672

Type(s) of Resistant Mechanism of This Drug

  EADR: Epigenetic Alteration of DNA, RNA or Protein

  MRAP: Metabolic Reprogramming via Altered Pathways

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Their Corresponding Diseases

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

Brain cancer [ICD-11: 2A00]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Smoothened homolog (SMO) [3]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Down-regulation

Differential expression of the molecule in resistant disease

• Classification of Disease: Brain cancer [ICD-11: 2A00]
• The Specified Disease: Neuroectodermal tumor
• The Studied Tissue: Brainstem tissue
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.31E-03; Fold-change: -1.34E-01; Z-score: -4.43E+00
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: SHH/GLI1 signaling pathway; Inhibition; hsa05217
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR326 exerts a tumor inhibition effect by decreasing the activity of the SHH/GLI1 pathway. miR326 could target the SMO oncogene to inhibit the biological behaviors and stemness of glioma cells.

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-miR-326 [3]

• Sensitive Disease: Glioblastoma [ICD-11: 2A00.02]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: SHH/GLI1 signaling pathway; Inhibition; hsa05217
• In Vitro Model: U251 cells; Brain; Homo sapiens (Human); CVCL_0021
• In Vitro Model: U87 cells; Brain; Homo sapiens (Human); CVCL_0022
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: miR326 exerts a tumor inhibition effect by decreasing the activity of the SHH/GLI1 pathway. miR326 could target the SMO oncogene to inhibit the biological behaviors and stemness of glioma cells.

Colorectal cancer [ICD-11: 2B91]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: microRNA-137 (miR-137) [4]

• Metabolic Type: Glutamine metabolism
• Sensitive Disease: Colorectal cancer [ICD-11: 2B91.1]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: DLD-1 cells; Colon; Homo sapiens (Human); CVCL_0248
• In Vitro Model: HCT-116 cells; Colon; Homo sapiens (Human); CVCL_0291
• In Vitro Model: HT-29 cells; Colon; Homo sapiens (Human); CVCL_0320
• In Vitro Model: LOVO cells; Colon; Homo sapiens (Human); CVCL_0399
• In Vitro Model: SW-480 cells; Colon; Homo sapiens (Human); CVCL_0546
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Using a microRNA (miRNA) microArray assay, miR-137, a tumor suppressor in colon cancer, was significantly induced by curcumin treatments in CRC cells. Bioinformatics analysis and a luciferase assay illustrated miR-137 directly targeted the 3' UTR of GLS mRNA. Rescue experiments demonstrated that miR-137-induced cisplatin sensitization was through targeting of GLS. Finally, curcumin treatment overcame cisplatin resistance through miR-137-mediated glutamine inhibition.

Liver cancer [ICD-11: 2C12]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-200a [2]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HepJ5 cells; Liver; Homo sapiens (Human); CVCL_RW48
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression ofmiR-200a/b in HepJ5 cells conferred enhanced resistance tocurcumin treatment compared with the control cells.

Key Molecule: hsa-mir-200b [2]

• Resistant Disease: Hepatocellular carcinoma [ICD-11: 2C12.2]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• In Vitro Model: HepJ5 cells; Liver; Homo sapiens (Human); CVCL_RW48
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: The overexpression ofmiR-200a/b in HepJ5 cells conferred enhanced resistance tocurcumin treatment compared with the control cells.

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Metabolic Reprogramming via Altered Pathways (MRAP)

Key Molecule: L-type amino acid transporter 2 (LAT2) [5]

• Metabolic Type: Glutamine metabolism
• Sensitive Disease: Cholangiocarcinoma [ICD-11: 2C12.00]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• In Vitro Model: KKU-213B cells; Liver; Homo sapiens (Human); CVCL_M264
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: Cell viability assay
• Mechanism Description: Moreover, in vivo experiments showed that a combination curcumin and gemcitabine significantly reduced tumor size, tumor growth rate and LAT2 expression in a gemcitabine-resistant CCA xenograft mouse model. Suppression of tumor progression in an orthotopic CCA hamster model provided strong support for clinical application. In conclusion, curcumin synergistically enhances gemcitabine efficacy against gemcitabine-resistant CCA by induction of apoptosis, partly via inhibiting LAT2/glutamine pathway.

Lung cancer [ICD-11: 2C25]

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: Urothelial cancer associated 1 (UCA1) [6]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell proliferation; Activation; hsa05200
• Cell Pathway Regulation: Wnt signaling pathway; Inhibition; hsa04310
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: qRT-PCR
• Experiment for Drug Resistance: CCK8 assay; BrdU assay; Flow cytometry assay
• Mechanism Description: Curcumin inhibited Wnt and mTOR pathways through down-regulation of UCA1.

Unusual Activation of Pro-survival Pathway (UAPP)

Key Molecule: Serine/threonine-protein kinase mTOR (mTOR) [6]

• Sensitive Disease: Lung cancer [ICD-11: 2C25.5]
• Molecule Alteration: Phosphorylation; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Activation; hsa04210
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• Cell Pathway Regulation: Wnt signaling pathway; Inhibition; hsa04310
• Cell Pathway Regulation: mTOR signaling pathway; Inhibition; hsa04150
• In Vitro Model: A549 cells; Lung; Homo sapiens (Human); CVCL_0023
• Experiment for Molecule Alteration: Western blot analysis
• Experiment for Drug Resistance: CCK8 assay; BrdU assay; Flow cytometry assay
• Mechanism Description: Curcumin inhibited Wnt and mTOR pathways through down-regulation of UCA1.

Breast cancer [ICD-11: 2C60]

Drug Resistance Data Categorized by Their Corresponding Mechanisms

Epigenetic Alteration of DNA, RNA or Protein (EADR)

Key Molecule: hsa-mir-21 [1]

• Resistant Disease: Breast cancer [ICD-11: 2C60.3]
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell apoptosis; Inhibition; hsa04210
• Cell Pathway Regulation: Cell invasion; Activation; hsa05200
• Cell Pathway Regulation: Cell migration; Activation; hsa04670
• In Vitro Model: MCF-7 cells; Breast; Homo sapiens (Human); CVCL_0031
• In Vitro Model: SkBR3 cells; Breast; Homo sapiens (Human); CVCL_0033
• In Vitro Model: MDA-MB-231 cells; Breast; Homo sapiens (Human); CVCL_0062
• Experiment for Molecule Alteration: RT-PCR
• Experiment for Drug Resistance: MTT assay; Transwell migration assay; Flow cytometric analysis
• Mechanism Description: Up-regulation of miR21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells. miR21 decreased apoptotic cells and increased cell migration capacity.

References

• Ref 1: Up-regulation of miR-21 decreases chemotherapeutic effect of dendrosomal curcumin in breast cancer cells. Iran J Basic Med Sci. 2017 Apr;20(4):350-359. doi: 10.22038/IJBMS.2017.8574.
• Ref 2: MicroRNA-200a/b influenced the therapeutic effects of curcumin in hepatocellular carcinoma (HCC) cells. Tumour Biol. 2013 Oct;34(5):3209-18. doi: 10.1007/s13277-013-0891-z. Epub 2013 Jun 13.
• Ref 3: MicroRNA-326 sensitizes human glioblastoma cells to curcumin via the SHH/GLI1 signaling pathway. Cancer Biol Ther. 2018 Apr 3;19(4):260-270. doi: 10.1080/15384047.2016.1250981. Epub 2018 Feb 22.
• Ref 4: Curcumin Synergizes with Cisplatin to Inhibit Colon Cancer through Targeting the MicroRNA-137-Glutaminase Axis. Curr Med Sci. 2022 Feb;42(1):108-117.
• Ref 5: Curcumin synergistically enhances the efficacy of gemcitabine against gemcitabine-resistant cholangiocarcinoma via the targeting LAT2/glutamine pathway. Sci Rep. 2024 Jul 11;14(1):16059.
• Ref 6: Curcumin inhibits proliferation and enhances apoptosis in A549 cells by downregulating lncRNA UCA1. Pharmazie. 2018 Jul 1;73(7):402-407. doi: 10.1691/ph.2018.8402.