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Flavokawain C inhibits proliferation and migration of liver cancer cells through FAK/PI3K/AKT signaling pathway.
- Source :
-
Journal of Cancer Research & Clinical Oncology . Mar2024, Vol. 150 Issue 3, p1-17. 17p. - Publication Year :
- 2024
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Abstract
- Purpose: This study investigated the potential applicability and the underlying mechanisms of flavokawain C, a natural compound derived from kava extracts, in liver cancer treatment. Methods: Drug distribution experiment used to demonstrate the preferential tissues enrichment of flavokawain C. Cell proliferation, apoptosis and migration effect of flavokawain C were determined by MTT, colony formation, EdU staining, cell adhesion, transwell, flow cytometry and western blot assay. The mechanism was explored by comet assay, immunofluorescence assay, RNA-seq-based Kyoto encyclopedia of genes and genomes analysis, molecular dynamics, bioinformatics analysis and western blot assay. The anticancer effect of flavokawain C was further confirmed by xenograft tumor model. Results: The studies first demonstrated the preferential enrichment of flavokawain C within liver tissues in vivo. The findings demonstrated that flavokawain C significantly inhibited proliferation and migration of liver cancer cells, induced cellular apoptosis, and triggered intense DNA damage along with strong DNA damage response. The findings from RNA-seq-based KEGG analysis, molecular dynamics, bioinformatics analysis, and western blot assay mechanistically indicated that treatment with flavokawain C notably suppressed the FAK/PI3K/AKT signaling pathway in liver cancer cells. This effect was attributed to the induction of gene changes and the binding of flavokawain C to the ATP sites of FAK and PI3K, resulting in the inhibition of their phosphorylation. Additionally, flavokawain C also displayed the strong capacity to inhibit Huh-7-derived xenograft tumor growth in mice with minimal adverse effects. Conclusions: These findings identified that flavokawain C is a promising anticancer agent for liver cancer treatment. [ABSTRACT FROM AUTHOR]
Details
- Language :
- English
- ISSN :
- 01715216
- Volume :
- 150
- Issue :
- 3
- Database :
- Academic Search Index
- Journal :
- Journal of Cancer Research & Clinical Oncology
- Publication Type :
- Academic Journal
- Accession number :
- 176061697
- Full Text :
- https://doi.org/10.1007/s00432-024-05639-z