Mechanistic Insight into the Autophagic and Apoptotic Activity of Kaempferol on Liver Cancer Cells.
ER-stress
HCC
apoptosis
autophagy
kaempferol
Journal
OncoTargets and therapy
ISSN: 1178-6930
Titre abrégé: Onco Targets Ther
Pays: New Zealand
ID NLM: 101514322
Informations de publication
Date de publication:
2024
2024
Historique:
received:
18
01
2024
accepted:
08
07
2024
medline:
29
7
2024
pubmed:
29
7
2024
entrez:
29
7
2024
Statut:
epublish
Résumé
The accumulation of poorly folded protein in the endoplasmic reticulum (ER) promotes ER stress and contributes to the pathogenesis of hepatocellular carcinoma (HCC). Current therapies have various adverse effects, therefore, laying the need for an alternative approach. Kaempferol (KP), a naturally occurring flavonoid, possesses potent anti-proliferative properties against various cancer cells. Nevertheless, its involvement in HCC remains relatively unexplored, particularly regarding its influence on apoptosis and autophagy pathways. The effect of KP on cell viability, and motility of Hep3B cells was evaluated by MTT, and scratch assay, respectively. Hoechst staining and FACS analysis were done to check the effect of KP on apoptosis and cell cycle progression. qRTPCR was used to evaluate the expression of several apoptosis and autophagy-related genes. KP was docked with several ER stress-related proteins involved in HCC to gain further insights into molecular mechanisms. The results of docking studies were validated with MD simulation and in vitro studies. Treatment with KP at different time intervals showed dose- and time-dependent growth inhibition of liver cancer cells. KP decreased motility and arrested the cell cycle at the G0/G1 phase in Hep3B cells. Additionally, in the context of HCC, the relationship between KP, apoptosis, and autophagy is significant. It induced apoptosis and autophagy in Hep3B cells by downregulating the expression of The study suggested KP as a potential chemopreventive agent for managing HCC by effectively inducing apoptosis and autophagy in Hep3B cells.
Sections du résumé
Background
UNASSIGNED
The accumulation of poorly folded protein in the endoplasmic reticulum (ER) promotes ER stress and contributes to the pathogenesis of hepatocellular carcinoma (HCC). Current therapies have various adverse effects, therefore, laying the need for an alternative approach. Kaempferol (KP), a naturally occurring flavonoid, possesses potent anti-proliferative properties against various cancer cells. Nevertheless, its involvement in HCC remains relatively unexplored, particularly regarding its influence on apoptosis and autophagy pathways.
Methods
UNASSIGNED
The effect of KP on cell viability, and motility of Hep3B cells was evaluated by MTT, and scratch assay, respectively. Hoechst staining and FACS analysis were done to check the effect of KP on apoptosis and cell cycle progression. qRTPCR was used to evaluate the expression of several apoptosis and autophagy-related genes. KP was docked with several ER stress-related proteins involved in HCC to gain further insights into molecular mechanisms. The results of docking studies were validated with MD simulation and in vitro studies.
Results
UNASSIGNED
Treatment with KP at different time intervals showed dose- and time-dependent growth inhibition of liver cancer cells. KP decreased motility and arrested the cell cycle at the G0/G1 phase in Hep3B cells. Additionally, in the context of HCC, the relationship between KP, apoptosis, and autophagy is significant. It induced apoptosis and autophagy in Hep3B cells by downregulating the expression of
Conclusion
UNASSIGNED
The study suggested KP as a potential chemopreventive agent for managing HCC by effectively inducing apoptosis and autophagy in Hep3B cells.
Identifiants
pubmed: 39071955
doi: 10.2147/OTT.S460359
pii: 460359
pmc: PMC11283267
doi:
Types de publication
Journal Article
Langues
eng
Pagination
579-601Informations de copyright
© 2024 Sharma et al.
Déclaration de conflit d'intérêts
The authors declare no conflicts of interest in this work.