Abstract
Kaempferol (Kae), a natural flavonoid, is widely distributed in fruits and vegetables. Previous studies have identified Kae as a possible cancer preventive and therapeutic agent. We found Kae to exhibit potent antiproliferation and anti-migration effects in human bladder cancer EJ cells. Kaempferol robustly induced apoptosis in EJ cells in a dose-dependent manner, as evidenced by increased cleavage of caspase-3. Furthermore, we found Kae-induced apoptosis in EJ cells to be associated with phosphatase and the tensin homolog deleted on the chromosome 10 (PTEN)/PI3K/Akt pathway. Kae significantly increased PTEN and decreased Akt phosphorylation. Kae-induced apoptosis was partially attenuated in PTEN-knockdown cells. Our findings indicate that Kae could be an alternative medicine for bladder cancer, based on a PTEN activation mechanism.
Highlights
Bladder cancer is one of the most common cancers in the world [1]
To find Kae’s effects on cell viability, we performed a Cell Counting Kit-8 (CCK-8) assay on bladder cancer EJ and T24 cells treated with Kae (20, 40, 80 or 160 μM) or dimethyl sulfoxide (DMSO, vehicle) for 24 h and 48 h
For the first time, that Kae inhibits proliferation, induces apoptosis and suppresses migration in EJ cells, and these effects are at least partially mediated by the PTEN/phosphatidyl inositol-3-kinase (PI3K)/Akt signaling pathway as a novel mechanism
Summary
Bladder cancer is one of the most common cancers in the world [1]. current treatments for bladder cancer—surgery, radiation therapy, chemotherapy or their combination—prolong survival time, bladder cancer tends to recur and progress. The effects of Kae on bladder cancer remain unclear. In this investigation of the antitumor effects of Kae on human bladder cancer cells, we found that Kae increases apoptosis and decreases invasion in human bladder cancer EJ cells. PTEN is critical in cell proliferation and apoptosis, predominantly through dephosphorylation of phosphatidylinositol (3,4,5)-trisphosphate (PIP3) and inhibition of the protein kinase B (Akt) signaling pathway [18]. Our results indicate that Kae induces apoptosis in bladder cancer EJ cells by affecting the PTEN/phosphatidyl inositol-3-kinase (PI3K)/Akt pathway. Kaempferol significantly increases PTEN expression and decreases Akt phosphorylation, which potentiates its antitumor effects in EJ cells
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