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Phellodendronoside A Exerts Anticancer Effects Depending on Inducing Apoptosis Through ROS/Nrf2/Notch Pathway and
Yanpo Si1,2, Chengcheng Hui1, Tao Guo1,2
1Department of Pharmacy, Henan University of Chinese Medicine, Zhengzhou, People's Republic of China.
Purpose:
To reveal the potential mechanism of PDA on hepatocellular carcinoma SMMC-7721 cells in vitro.
Methods:
The cytotoxic activity, colony formation, cell cycle distribution, apoptosis and their associated protein analysis, intracellular reactive oxygen species (ROS) and Ca2+ levels, proteins in Nrf2 and Ntoch pathways and metabolite profiles of PDA against hepatocellular carcinoma were investigated.
Results:
PDA with cytotoxic activity inhibited cell proliferation and migration, increased intracellular ROS, Ca2+ levels and MCUR1 protein expression in a dose-dependent manner, caused cell cycle arrest in the S phase and induced apoptosis via adjusting the levels of Bcl-2, Bax, and Caspase 3 proteins, and inhibited the activation of Notch1, Jagged, Hes1, Nrf2 and HO-1 proteins. Metabonomics data showed that PDA significantly regulated 144 metabolite levels tend to be normal level, especially carnitine derivatives, bile acid metabolites associated with hepatocellular carcinoma, and mainly enriched in ABC transporter, arginine and proline metabolism, primary bile acid biosynthesis, Notch signaling pathway, etc, and proved that PDA markedly adjusted Notch signaling pathway.
Conclusion:
PDA exhibited the proliferation inhibition of SMMC-7721 cells by inhibiting ROS/Nrf2/Notch signaling pathway and significantly affected the metabolic profile, suggesting PDA could be a potential therapeutic agent for patients with hepatocellular carcinoma.
Insights
This study reveals that Phellodendri Cortex extract (PDA) inhibits hepatocellular carcinoma cell proliferation by targeting the ROS/Nrf2/Notch signaling pathway and altering metabolic profiles, suggesting its potential as a therapeutic agent.
Area of Science:
- Pharmacology
- Cell Biology
- Biochemistry
Background:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Identifying novel therapeutic agents for HCC is crucial.
Purpose of the Study:
- To elucidate the mechanism by which Phellodendri Cortex extract (PDA) affects hepatocellular carcinoma SMMC-7721 cells in vitro.
- To investigate PDA's potential as a therapeutic agent for HCC.
Main Methods:
- Assessed cytotoxic activity, colony formation, cell cycle distribution, and apoptosis.
- Analyzed intracellular reactive oxygen species (ROS) and Ca2+ levels.
- Investigated protein expression in Nrf2 and Notch pathways and metabolite profiles.
Main Results:
- PDA demonstrated dose-dependent inhibition of cell proliferation and migration, increased ROS and Ca2+ levels, and induced apoptosis.
- PDA suppressed the activation of key proteins in the Nrf2 and Notch signaling pathways.
- Metabonomic analysis revealed PDA significantly regulated metabolites, particularly those related to bile acid biosynthesis and carnitine derivatives, and modulated the Notch signaling pathway.
Conclusions:
- PDA inhibits HCC cell proliferation by targeting the ROS/Nrf2/Notch signaling pathway.
- PDA significantly alters the metabolic profile of HCC cells.
- PDA shows promise as a potential therapeutic agent for hepatocellular carcinoma.
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