18α-Glycyrrhetinic Acid Induces Apoptosis of HL-60 Human Leukemia Cells through Caspases- and Mitochondria-Dependent Signaling Pathways.

In this study we investigate the molecular mechanisms of caspases and mitochondria in the extrinsic and intrinsic signal apoptosis pathways in human leukemia HL-60 cells after in vitro exposure to 18α-glycyrrhetinic acid (18α-GA). Cells were exposed to 18α-GA at various concentrations for various time periods and were harvested for flow cytometry total viable cell and apoptotic cell death measurements. Cells treated with 18α-GA significantly inhibited cell proliferation and induced cell apoptosis in a dose-dependent manner, with an IC50 value of 100 µM at 48 h. The cell growth inhibition resulted in induction of apoptosis and decreased the mitochondria membrane potential (ΔΨm) and increased caspase-8, -9 and -3 activities. Furthermore, cytochrome c and AIF were released from mitochondria, as shown by western blotting and confirmed by confocal laser microscopy. Western blotting showed that 18α-GA increased the levels of pro-apoptotic proteins such as Bax and Bid and decreased the anti-apoptotic proteins such as Bcl-2 and Bcl-xl, furthermore, results also showed that 18α-GA increased Fas and Fas-L which are associated with surface death receptor in HL-60 cells. Based on those observations, the present study supports the hypothesis that 18α-GA-induced apoptosis in HL-60 cells involves the activation of the both extrinsic and intrinsic apoptotic pathways.

Perform kicking with or without jumping: joint coordination and kinetic differences between Taekwondo back kicks and jumping back kicks.

We investigated joint coordination differences between Taekwondo back kicks and jumping back kicks, and how jumping (in performing the latter) would alter engaging ground reaction forces (GRF) in executing kicking. Ten skilful athletes volunteered to perform both kinds of kicking within the shortest time for three successful trials. Three high-speed cameras and two force platforms were used for data collection, and the trial with the shortest execution time was selected for analysis. Movements were divided into the rotation and attack phases. With comparable execution time and maximum joint linear/angular speeds, back kicks and jumping back kicks differ mainly in larger GRF in the latter, and in greater target acceleration in the former probably because the support leg prevented athletes' rebounding after impact. In addition, more prominent antiphase and in-phase coordination between the shoulder segment and knee joint, and elongated rotation phase were found in jumping back kicks. Larger GRF values in jumping back kicks were generated for jump take-off rather than for a more powerful attack. In back kicks although the support leg remained ground contact, greatly decreased GRF in the attack phase suggested that the support leg mainly served as a rotation axis.

Fisetin induces apoptosis in human cervical cancer HeLa cells through ERK1/2-mediated activation of caspase-8-/caspase-3-dependent pathway.

Fisetin is a naturally occurring flavonoid that has been reported to inhibit the proliferation and to induce apoptotic cell death in several tumor cells. However, the apoptosis-inducing effect of fisetin on tumor cell lines was investigated besides HeLa cells. In this study, we found that fisetin induced apoptosis of HeLa cells in a dose- and time-dependent manner, as evidenced by nuclear staining of 4'-6-Diamidino-2-phenylindole (DAPI), flow cytometry assay, and Annexin-V/PI double-labeling. In addition, fisetin triggered the activations of caspases-3 and -8 and the cleavages of poly (ADP-ribose) polymerase, resulting in apoptosis induction. Moreover, treatment of HeLa cells with fisetin induced a sustained activation of the phosphorylation of ERK1/2, and inhibition of ERK1/2 by PD98059 (MEK1/2 inhibitor) or transfection with the mutant ERK1/2 expression vector significantly abolished the fisetin-induced apoptosis through the activation of caspase-8/-3 pathway. The in vivo xenograft mice experiments revealed that fisetin significantly reduced tumor growth in mice with HeLa tumor xenografts. In conclusion, our results indicated that fisetin exhibited anti-cancer effect and induced apoptosis in HeLa cell lines both in vitro and in vivo.

Effect of arm swing on single-step balance recovery.

Balance recovery techniques are useful not only in preventing falls but also in many sports activities. The step strategy plays an important role especially under intense perturbations. However, relatively little is known about the effect of arm swing on stepping balance recovery although considerable arm motions have been observed. The purpose of this study was to examine how the arms influence kinematic and kinetic characteristics in single-step balance recovery. Twelve young male adults were released from three forward-lean angles and asked to regain balance by taking a single step under arm swing (AS) and arm constrained (AC) conditions. It was found that unconstrained arms had initial forward motion and later upward motion causing increased moment of inertia of the body, which decreased falling angular velocity and allowed more time for stepping. The lengthened total balance time included weight transfer and stepping time, although duration increase in the latter was significant only at the largest lean angle. In contrast, step length, step velocity, and vertical ground reaction forces on the stepping foot were unaffected by arm swing. Future studies are required to investigate optimal movement strategies for the arms to coordinate with other body segments in balance recovery and injury reduction.

Fisetin inhibits migration and invasion of human cervical cancer cells by down-regulating urokinase plasminogen activator expression through suppressing the p38 MAPK-dependent NF-κB signaling pathway.

Fisetin (3,3',4',7-tetrahydroxyflavone), a naturally occurring flavonoid, has been reported to inhibit proliferation and induce apoptosis in several cancer types. However, its effect on the anti-metastatic potential of cervical cancer cells remains unclear. In the present study, we found that fisetin inhibits the invasion and migration of cervical cancer cells. The expression and activity of urokinase plasminogen activator (uPA) was significantly suppressed by fisetin in a dose-dependent manner. We also demonstrated that fisetin reduces the phosphorylation of p38 MAPK, but not that of ERK1/2, JNK1/2, or AKT. Addition of a p38 MAPK inhibitor, SB203580, further enhanced the inhibitory effect of fisetin on the expression and activity of uPA and the invasion and motility in cervical cancer cells. Fisetin suppressed the TPA (tetradecanoylphorbol-13-acetate)-induced activation of p38 MAPK and uPA, and inhibited the TPA-enhanced migratory and invasive abilities. Furthermore, the promoter activity of the uPA gene was dramatically repressed by fisetin, which disrupted the nuclear translocation of NF-κB and its binding amount on the promoter of the uPA gene, and these suppressive effects could be further enhanced by SB203580. This study provides strong evidence for the molecular mechanism of fisetin in inhibiting the aggressive phenotypes by repression of uPA via interruption of p38 MAPK-dependent NF-κB signaling pathway in cervical cancer cells and thus contributes insight to the potential of using fisetin as a therapeutic strategy against cervical cancer by inhibiting migration and invasion.