[Human hepatocarcinoma cell apoptosis induced by toosendanin through mitochondria-dependent pathway]
Objective:
To explore the effects of toosendanin in inducing apoptosis of human hepatocarcinoma cell line SMMC-7721 and Hep3B, and its influence on the related genes, Bcl-2, Bax and Fas.
Methods:
The inhibitory rate of cell proliferation and cell growth curve were detected by MTT assay; morphological changes of cells were observed by inverted microscope; early stage apoptosis rate were detected by Annexin V-FITC/PI assay; relative activities of Caspase-3,-8 and-9 were analyzed by spectrophotometry; and the expressions of Bcl-2, Bax and Fas were detected using immunohistochemistry assay.
Results:
Toosendanin presented significant inhibitory effect on proliferation of hepatocarcinoma cells in a time- and dose-dependent manner. After toosendanin treatment, the amount of cells was significantly reduced, shrunk in size and rounded in shape, with decreased adhesion ability. The apoptosis rates of SMMC-7721 cells and Hep3B cells treated with 0.5 micromol/L toosendanin for 72 h were 21.55% and 18.35% respectively, which were reduced after z-VAD-fmk (inhibitor of Caspase) treatment. The activities of Caspase-3,-8 and -9 all markedly enhanced after treatment in SMMC-7721 cells, while in Hep3B cells, activities of Caspase-3 and -9 enhanced, but that of Caspase-8 unchanged. As compared with the control group, after toosendanin treatment, expression of Bcl-2 decreased, and that of Bax and Fas increased in SMMC-7721 cells; but in Hep3B cells the expression of Bcl-2 decreased, that of Bax increased, and expression of Fas unchanged.
Conclusions:
Toosendanin could inhibit the proliferation and induce the apoptosis of both P53 and P53 human hepatocarcinoma cells, which involved the participation of mitochondria-dependent pathway. So it may be a kind of natural anti-cancer drug, playing its effect through P53 independent pathway.
Insights
Toosendanin inhibits human hepatocarcinoma cell growth and induces apoptosis through the mitochondria-dependent pathway. This natural compound may serve as a potential anti-cancer drug, acting independently of P53.
Area of Science:
- Pharmacology
- Molecular Biology
- Oncology
Context:
- Hepatocellular carcinoma (HCC) remains a significant global health challenge.
- Identifying novel therapeutic agents for HCC is crucial.
- Toosendanin, a natural compound, has shown potential anti-cancer properties.
Purpose:
- To investigate the effects of toosendanin on human hepatocarcinoma cell lines SMMC-7721 and Hep3B.
- To determine toosendanin's role in inducing apoptosis and its influence on key regulatory genes (Bcl-2, Bax, Fas).
Summary:
- Toosendanin demonstrated significant, dose- and time-dependent inhibition of hepatocarcinoma cell proliferation.
- Morphological changes and increased apoptosis rates (21.55% in SMMC-7721, 18.35% in Hep3B) were observed.
- Toosendanin modulated the expression of Bcl-2, Bax, and Fas, and enhanced Caspase activity, indicating apoptosis induction via the mitochondria-dependent pathway.
- The anti-cancer effects were observed in both P53 wild-type and P53-deficient cells, suggesting a P53-independent mechanism.
Impact:
- Toosendanin exhibits potential as a natural anti-cancer drug for hepatocellular carcinoma.
- The findings provide insights into the molecular mechanisms of toosendanin-induced apoptosis.
- This research may pave the way for developing new therapeutic strategies against HCC.
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