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Published:
Sep 15, 2023DOI:
10.4314/tjpr.v22i8.2Keywords:
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Main Article Content
Cardamonin suppresses glycolysis and induces oxidative stress by inhibiting PI3K/AKT/mTOR pathway in bladder cancer cells
Abstract
Purpose: To evaluate the effect and underlying mechanisms of action of cardamine on the progression of bladder cancer (BC).
Methods: Human bladder epithelium immortalized cell line (SV-HUC-1) and human bladder cancer (BC) cell lines (T24 and UM-UC-3) were used in this investigation. They were treated with cardamine at concentrations of 0, 15, 30, 60 or 120 μmol/L. Cell viability was determined using cell counting kit 8
(CCK-8) assay while 5-ethynyl-2'-deoxyuridine (Edu) assay was used to assess cell proliferation. Cell apoptosis as well as reactive oxygen species (ROS) accumulation were determined by flow cytometry whereas glucose uptake, adenosine triphosphate (ATP) level and lactate production were determined using their respective assay kits. Furthermore, the expression levels of nuclear factor level (erythroidderived 2)-like 2 (Nrf2), NAD(P)H, quinone oxidoreductase 1 (NQO1), protein kinase B (AKT), phosphorylated-AKT (p-AKT), phosphatidylinositol 3-kinase (PI3K), p-PI3K, mechanistic target of rapamycin kinase (mTOR) and p-mTOR were evaluated by western blot analysis.
Results: Cardamine significantly reduced cell viability and inhibited cell proliferation in BC cells in a dose-dependent manner, but did not affect human normal cells. In addition, treatment with the compound induced apoptosis in BC cells; the higher the concentration, the higher the apoptosis level. Besides, cardamine administration suppressed aerobic glycolysis, and decreased the nuclear factor level (Nrf2) level, thereby increasing ROS production in a concentration-dependent manner.
Furthermore, it blocked the activation of PI3K/AKT/mTOR signal cascade.
Conclusion: Cardamine inhibits glycolysis and PI3K/AKT/mTOR pathway, and also promotes apoptosis as well as oxidative stress in BC cells. Thus, the compound is a potential therapeutic reagent for BC.
