Mechanism of Quercetin and Luteolin on Colon Cancer Metastasis: Network Pharmacological Study and Experimental
Shi-Wei Wu1, Jin-Fang Chen1, Zi-Man Shi1
1Cancer Institute, Department of Oncology, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, P. R. China.
Abstract:
Quercetin (QCT) and luteolin (LTL) are anticancer herbal compounds. However, their combined effects on colon cancer metastasis remain unknown. This study explored the effects and mechanisms of QCT and LTL against colon cancer metastasis using network pharmacology and experimental validation. We systematically screened 74 QCT and LTL targets from the TCMSP, HERB, SwissTargetPrediction, TCGA, and GeneCards databases, which intersected with colon cancer metastasis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis were performed to investigate the biological processes and pathways of QCT and LTL. These analyses revealed that QCT and LTL modulate 119 pathways, and that of these, the PTK2/PI3K/Akt pathway was associated with resistance to colorectal cancer metastasis. Experimental validation demonstrated that the combination of QCT and LTL inhibited the anchorage-independent growth, adhesion, migration, and invasion of CT26 cells. The combined treatment also induced caspase-dependent anoikis in CT26 cells. In addition, QCT and LTL synergistically inhibited the lung metastasis of CT26 colon cancer in vivo. Furthermore, Western blot analysis and immunohistochemical detection identified that QCT and LTL inhibited the phosphorylation of PTK2/PI3K/Akt. These findings provide a basis for the application of QCT and LTL for the treatment of colon cancer metastasis.
Insights
Quercetin (QCT) and luteolin (LTL) inhibit colon cancer metastasis by targeting the PTK2/PI3K/Akt pathway. This combination therapy shows promise for treating colorectal cancer metastasis.
Area of Science:
- Natural product chemistry
- Oncology
- Molecular biology
Background:
- Quercetin (QCT) and luteolin (LTL) are natural compounds with known anticancer properties.
- The combined therapeutic effects of QCT and LTL on colon cancer metastasis have not been previously investigated.
- Colon cancer metastasis remains a significant challenge in patient treatment and survival.
Purpose of the Study:
- To investigate the combined effects of QCT and LTL on colon cancer metastasis.
- To elucidate the underlying molecular mechanisms of QCT and LTL action against colon cancer metastasis.
- To validate the therapeutic potential of QCT and LTL in preclinical models.
Main Methods:
- Network pharmacology approach to identify targets and pathways.
- Bioinformatic analyses including Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment.
- In vitro experimental validation using CT26 colon cancer cells (anchorage-independent growth, adhesion, migration, invasion, anoikis).
- In vivo studies assessing lung metastasis in a CT26 colon cancer model.
- Western blot and immunohistochemical analyses to confirm pathway modulation.
Main Results:
- QCT and LTL targets were screened, revealing modulation of 119 pathways, notably the PTK2/PI3K/Akt pathway.
- Combined QCT and LTL significantly inhibited CT26 cell proliferation, adhesion, migration, and invasion.
- The synergistic treatment induced caspase-dependent anoikis and suppressed lung metastasis of colon cancer in vivo.
- QCT and LTL were found to inhibit the phosphorylation of the PTK2/PI3K/Akt signaling pathway.
Conclusions:
- QCT and LTL exhibit synergistic anticancer effects against colon cancer metastasis.
- The PTK2/PI3K/Akt pathway is a key mediator of QCT and LTL's anti-metastatic activity.
- This study provides a strong scientific rationale for developing QCT and LTL as a combination therapy for colon cancer metastasis.
