Kaempferol activates G2-checkpoint of the cell cycle resulting in mitochondria-dependent apoptosis in human acute leukemia Jurkat T cells. - GreenMedInfo Summary
Kaempferol activates G2-checkpoint of the cell cycle resulting in G2-arrest and mitochondria-dependent apoptosis in human acute leukemia Jurkat T cells.
J Microbiol Biotechnol. 2015 Dec 23. Epub 2015 Dec 23. PMID: 26699757
Ki Yun Kim
The effect of kaempferol (3,5,7,4-tetrahydroxy-flavone), a flavonoid compound which was identified in barnyard millet (Echinochloa crus-galli var. frumentacea) grains, on G2-checkpoint and apoptotic pathways was investigated in human acute leukemia Jurkat T cell clone stably transfected with an empty vector (J/Neo) or a Bcl-xL expression vector (J/Bcl-xL). Exposure of J/Neo cells to kaempeferol caused cytotoxicity, activation of ATM/ATR-Chk1/Chk2 pathway, activating phosphorylation of p53 (Ser-15), inhibitory phosphorylation of Cdc25C (Ser-216), and inactivation of cyclin-dependent kinase 1 (Cdk1), and resultant G2-arrest of the cell cycle. Under these conditions, apoptotic events including upregulation of Bak and PUMA levels, Bak activation, mitochondrial membrane potential (Δpsim) loss, activation of caspase-9, -8 and -3, anti-poly (ADP-ribose) polymerase (PARP) cleavage, and accumulation of apoptotic sub-G1 cells were induced, without accompanying necrosis. However, these apoptotic events, except for upregulation of Bak and PUMA levels, were completely abrogated in J/Bcl-xL cells overexpressing Bcl-xL, suggesting that the G2-arrest and the Bcl-xL-sensitive mitochondrial apoptotic events were induced, in parallel, as downstream events of the DNA damage-mediated G2-checkpoint activation. Together these results demonstrate that kaempferol-mediated antitumor activity toward Jurkat T cells was attributable to G2-checkpoint activation, which caused not only G2-arrest of the cell cycle but also activating phosphorylation of p53 (Ser-15) and subsequent induction of mitochondria-dependent apoptotic events including Bak and PUMA upregulations, Bak activation, Δpsim loss, and caspase cascade activation.