Flavonoids from Orostachys Japonicus A. Berger Induces Caspase-dependent Apoptosis at Least Partly through Activation of p38 MAPK Pathway in U937 Human Leukemic Cells

Background: Orostachys japonicus A. Berger (A. Berger) is commonly used as a folk remedy for cancertherapy. However, the mechanisms of its anti-cancer activity are poorly investigated in human cancer cells. Inthis study, we investigated whether flavonoids extracted from Orostachys japonicus A. Berger (FEOJ) mighthave anticancer effects in human leukemia cells, focusing on cell death mechanisms. Materials and
Methods:U937 human leukemic cancer cells were used.
Results: FEOJ induced apoptosis in a dose-dependent manner inhuman U937 cancer cells. Flow cytometry revealed significant accumulation of cells with sub-G1 DNA contentat the concentrations of 200 μg/mL and 400 μg/mL. FEOJ-induced apoptosis was caspase-dependent throughloss of mitochondrial membrane potential (MMP, ΔΨm) in human U937 cancer cells, which might be associatedwith suppression of Bcl-2 and XIAP proteins. FEOJ induced the p38 MAPK signaling pathway, playing at leastin part an important role in FEOJ-induced apoptosis.
Conclusions: This study suggested that FEOJ may inducecaspase-dependent apoptosis in human leukemic cells by regulating MMP (ΔΨm) through suppressing Bcl-2and X-IAP. In addition, the results indicated that upstream p38 MAPK signaling regulates the apoptotic effectof FEOJ. This study provides evidence that FEOJ might have anti-cancer potential for human leukemic cells.