ReferenceID 4963
Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor
Br J Pharmacol
BACKGROUND AND PURPOSE: Colorectal cancer is the third most common cancer worldwide. HER2 and HER3 are two members of human epidermal receptor family of tyrosine kinase receptors (RTKs) and associated with poor survival
Relationship Network
Interactive first-hop connections across herbs, ingredients, formulas, targets, diseases, symptoms, syndromes, evidence, and monographs.
Click a node to open it in a new tab
Ingredient: 1Reference: 1Links: 1
Arranging relationship network...
Record Fields
Scalar fields from the final reference record.
- Reference Id
- 4963
- Evidence Id
- 21553
- Core Evidence Id
- 21553
- Source Reference Id
- 3174
- Herb2 Reference Id
- HBREF003971
- Subject Paper Key
- HBIN021522_33443775
- Pubmed Id
- 33443775
- Doi
- 10.1111/bph.15372
- Paper Title
- Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor
- Paper Abstract
- BACKGROUND AND PURPOSE: Colorectal cancer is the third most common cancer worldwide. HER2 and HER3 are two members of human epidermal receptor family of tyrosine kinase receptors (RTKs) and associated with poor survival in colorectal cancer. They have been observed as important therapeutic targets in various types of cancer. Corosolic acid, a natural pentacyclic triterpene, has been demonstrated to have a significant anti-cancer activity. However, the target of corosolic acid has not yet been explored. This study aimed to reveal the direct targets of corosolic acid underlying its anti-cancer activities. EXPERIMENTAL APPROACH: The targets of corosolic acid were revealed by the phospho-RTK array, bio-layer interferometry, co-immunoprecipitation, and proximity ligation assay. The inhibitory action of corosolic acid on HER2/HER3 heterodimerization and related downstream signalling were investigated in HCT116 and SW480 cells. In addition, the chemo-preventive effects of corosolic acid were validated in both HCT116 xenograft model and AOM/DSS model. KEY RESULTS: Our results demonstrated that corosolic acid could prevent NRG1-induced HER2/HER3 heterodimerization and suppress the phosphorylation of both HER2 and HER3. Furthermore, HER2 and HER3 could regulate the downstream signalling pathways of RalA/RalBP1/CDK1 and PI3K/Akt/PKA, respectively, resulting in the changes in phosphorylation of Drp1 and mitochondrial dynamics. corosolic acid exhibited anti-cancer activity in both HCT116 xenograft model and AOM/DSS model. CONCLUSIONS AND IMPLICATIONS: Collectively, our results demonstrated corosolic acid directly targeted HER2 and HER3 heterodimerization and inhibited mitochondrial fission via regulating RalA/RalBP1/CDK1 and PI3K/Akt/PKA pathways, revealing a novel mechanism underlying the beneficial effects of corosolic acid on colorectal cancer.
- Journal
- Br J Pharmacol
- Publish Year
- 2021
- Experiment Subject
- human; sw480 cells
- Experiment Type
- Cell Experiment
- Phenotype Related
- Colorectal Cancer; Cancer
- Paper Title Cn
- Paper Title En
- Corosolic acid inhibits colorectal cancer cells growth as a novel HER2/HER3 heterodimerization inhibitor
- Bilingual Status
- semi_complete