Isorhamnetin Suppresses Human Gastric Cancer Cell Proliferation through Mitochondria-Dependent Apoptosis
Yehua Li1, Baoqiang Fan1, Ning Pu1
1College of Life Science, Northwest Normal University, Lanzhou 730070, China.
Abstract:
Derivates of natural products have been wildly utilized in the treatment of malignant tumors. Isorhamnetin (ISO), a most important active ingredient derived from flavonoids, shows great potential in tumor therapy. However, the therapeutic effects of ISO on gastric cancer (GC) remain unclear. Here, we demonstrate that ISO treatment dramatically inhibited the proliferation of two types of GC cells (AGS-1 and HGC-27) both in vitro and in vivo in time- and dose-dependent manners. These results are consistent with the transcriptomic analysis of ISO-treated GC cells, which yielded hundreds of differentially expressed genes that were enriched with cell growth and apoptosis. Mechanically, ISO treatment initiated the activation of caspase-3 cascade and elevated the expression of mitochondria-associated Bax/Bcl-2, cytosolic cytochrome c, followed by the activation of the cleavage of caspase-3 as well as poly ADP-ribose polymerase (PARP), resulting in the severe reduction of the mitochondrial potential and the accumulation of reactive oxygen species (ROS), while pre-treatment of the caspase-3 inhibitor could block the anti-tumor effect. Therefore, these results indicate that ISO treatment induces the apoptosis of GC cells through the mitochondria-dependent apoptotic pathway, providing a potential strategy for clinical GC therapy.
Insights
Isorhamnetin (ISO) effectively inhibits gastric cancer (GC) cell proliferation by inducing apoptosis through the mitochondria-dependent pathway. This natural compound shows promise as a potential therapeutic strategy for gastric cancer treatment.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Natural product derivatives are crucial in cancer therapy.
- Isorhamnetin (ISO), a flavonoid, exhibits potential anti-tumor properties.
- The efficacy of ISO in gastric cancer (GC) requires further investigation.
Purpose of the Study:
- To investigate the anti-cancer effects of Isorhamnetin (ISO) on gastric cancer (GC) cells.
- To elucidate the underlying molecular mechanisms of ISO's action in GC.
- To assess the therapeutic potential of ISO for GC treatment.
Main Methods:
- In vitro and in vivo proliferation assays using GC cell lines (AGS-1, HGC-27).
- Transcriptomic analysis to identify differentially expressed genes.
- Western blotting and assays to evaluate apoptosis-related proteins (caspase-3, Bax, Bcl-2, PARP), mitochondrial potential, and reactive oxygen species (ROS).
Main Results:
- ISO significantly inhibited GC cell proliferation in a time- and dose-dependent manner.
- Transcriptomic analysis revealed enrichment of genes related to cell growth and apoptosis.
- ISO activated the caspase-3 cascade, altered Bax/Bcl-2 expression, increased cytosolic cytochrome c, and reduced mitochondrial potential, leading to apoptosis.
Conclusions:
- ISO induces apoptosis in gastric cancer cells via the mitochondria-dependent pathway.
- The caspase-3 cascade plays a critical role in ISO-mediated GC cell death.
- ISO represents a potential therapeutic agent for clinical gastric cancer treatment.
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