Molecule Information

General Information of the Molecule (ID: Mol00623)

• Name: Succinate dehydrogenase [ubiquinone] iron-sulfur subunit (SDHB) ,Homo sapiens
• Synonyms: Iron-sulfur subunit of complex II; Ip; SDH; SDH1
• Molecule Type: Protein
• Gene Name: SDHB
• Gene ID: 6390
• Location: chr1:17018722-17054032[-]
• Sequence:
  MAAVVALSLRRRLPATTLGGACLQASRGAQTAAATAPRIKKFAIYRWDPDKAGDKPHMQT
  YEVDLNKCGPMVLDALIKIKNEVDSTLTFRRSCREGICGSCAMNINGGNTLACTRRIDTN
  LNKVSKIYPLPHMYVIKDLVPDLSNFYAQYKSIEPYLKKKDESQEGKQQYLQSIEEREKL
  DGLYECILCACCSTSCPSYWWNGDKYLGPAVLMQAYRWMIDSRDDFTEERLAKLQDPFSL
  YRCHTIMNCTRTCPKGLNPGKAIAEIKKMMATYKEKKASV
• Function: Iron-sulfur protein (IP) subunit of the succinate dehydrogenase complex (mitochondrial respiratory chain complex II), responsible for transferring electrons from succinate to ubiquinone (coenzyme Q).
• Uniprot ID: SDHB_HUMAN
• Ensembl ID: ENSG00000117118
• HGNC ID: HGNC:10681

Kingdom: Metazoa
Phylum: Chordata
Class: Mammalia
Order: Primates
Family: Hominidae
Genus: Homo
Species: Homo sapiens

Type(s) of Resistant Mechanism of This Molecule

  UAPP: Unusual Activation of Pro-survival Pathway

Drug Resistance Data Categorized by Drug

Approved Drug(s) 2 drug(s) in total

Doxorubicin

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Liver cancer [1]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Curcumin was able to induce SDH expression and repress the IDH3a in HepG2 cells both in a normal or elevated level of glucose. Such changes in SDH and IDH3a levels can bring a reduction in the succinate accumulation and hindering the succinate-HIF-1alpha axis. The augmented expression of HIF-1alpha in high glucose conditions was resisted by curcumin. HIF-1alpha is known for metabolic regulation in malignant cells, their hyperglycolytic behavior, and the onset of chemoresistance. HIF-1 exerts protumor effects through the upregulated expression of enzymes and transporters favoring the hyperglycolytic and therapy-resistant phenotype.

Disease Class: Liver cancer [1]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Doxorubicin
• Molecule Alteration: Expression; Down-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Curcumin mediated the amputation of chemoresistance by repressing the hyperglycolytic behavior of malignant cells via modulated expression of metabolic enzymes (HkII, PFk1, GAPDH, PkM2, LDH, SDH, IDH, and FASN), transporters (GLUT-1, MCT-1, and MCT-4), and their regulators. Along altered constitution of extracellular milieu, these molecular changes culminated into improved drug accumulation, chromatin condensation, and induction of cell death.

Methotrexate

Drug Sensitivity Data Categorized by Their Corresponding Mechanisms

Unusual Activation of Pro-survival Pathway (UAPP)

Disease Class: Liver cancer [1]

• Sensitive Disease: Liver cancer [ICD-11: 2C12.6]
• Sensitive Drug: Methotrexate
• Molecule Alteration: Expression; Up-regulation
• Experimental Note: Revealed Based on the Cell Line Data
• Cell Pathway Regulation: Cell proliferation; Inhibition; hsa05200
• In Vitro Model: HepG2 cells; Liver; Homo sapiens (Human); CVCL_0027
• Experiment for Molecule Alteration: Western blotting analysis
• Experiment for Drug Resistance: MTT assay
• Mechanism Description: Curcumin was able to induce SDH expression and repress the IDH3a in HepG2 cells both in a normal or elevated level of glucose. Such changes in SDH and IDH3a levels can bring a reduction in the succinate accumulation and hindering the succinate-HIF-1alpha axis. The augmented expression of HIF-1alpha in high glucose conditions was resisted by curcumin. HIF-1alpha is known for metabolic regulation in malignant cells, their hyperglycolytic behavior, and the onset of chemoresistance. HIF-1 exerts protumor effects through the upregulated expression of enzymes and transporters favoring the hyperglycolytic and therapy-resistant phenotype.

Disease- and Tissue-specific Abundances of This Molecule

ICD Disease Classification 02

Liver cancer [ICD-11: 2C12]

Differential expression of molecule in resistant diseases

• The Studied Tissue: Liver
• The Specified Disease: Liver cancer
• The Expression Level of Disease Section Compare with the Healthy Individual Tissue: p-value: 1.20E-07; Fold-change: -4.00E-01; Z-score: -1.19E+00
• The Expression Level of Disease Section Compare with the Adjacent Tissue: p-value: 5.83E-24; Fold-change: -2.72E-01; Z-score: -1.02E+00
• The Expression Level of Disease Section Compare with the Other Disease Section: p-value: 3.23E-03; Fold-change: -5.99E-01; Z-score: -3.53E+00

References

• Ref 1: Counteracting Action of Curcumin on High Glucose-Induced Chemoresistance in Hepatic Carcinoma Cells. Front Oncol. 2021 Oct 6;11:738961. doi: 10.3389/fonc.2021.738961. eCollection 2021.