Kaempferol is a natural
flavonoid. Previous studies have reported that
kaempferol has anti-proliferation activities and induces apoptosis in many
cancer cell lines. However, there are no reports on human
osteosarcoma. In this study, we investigate the anti-
cancer effects and molecular mechanisms of
kaempferol in human
osteosarcoma cells. Our results demonstrate that
kaempferol significantly reduces cell viabilities of U-2 OS, HOB and 143B cells, especially U-2 OS cells in a dose-dependent manner, but exerts low cytotoxicity on human fetal osteoblast progenitor hFOB cells. Comet assay,
DAPI staining and
DNA gel electrophoresis confirm the effects of DNA damage and apoptosis in U-2 OS cells. Flow cytometry detects the increase of cytoplasmic Ca(2+) levels and the decrease of mitochondria membrane potential. Western blotting and fluorogenic enzymatic assay show that
kaempferol treatment influences the time-dependent expression of
proteins involved in the endoplasmic reticulum stress pathway and mitochondrial signaling pathway. In addition, pretreating cells with
caspase inhibitors,
BAPTA or
calpeptin before exposure to
kaempferol increases cell viabilities. The anti-
cancer effects of
kaempferol in vivo are evaluated in BALB/c(nu/nu) mice inoculated with U-2 OS cells, and the results indicate inhibition of
tumor growth. In conclusion,
kaempferol inhibits human
osteosarcoma cells in vivo and in vitro.