alpha-Tocopheryl succinate potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in human H460 lung cancer cells

Paclitaxel is one of the chemotheraputic drugs widely used for the treatment of nonsmall cell lung cancer (NSCLC) patients. Here, we tested the ability of alpha-tocopheryl succinate (TOS), another promising anticancer agent, to enhance the paclitaxel response in NSCLC cells. We found that sub-apoptotic doses of TOS greatly enhanced paclitaxel-induced growth suppression and apoptosis in the human H460 NSCLC cell lines. Our data revealed that this was accounted for primarily by an augmented cleavage of poly(ADP-ribose) polymerase (PARP) and enhanced activation of caspase-8. Pretreatment with z-VAD-FMK (a pan-caspase inhibitor) or z-IETD-FMK (a caspase-8 inhibitor) blocked TOS/paclitaxel cotreatment-induced PARP cleavage and apoptosis, suggesting that TOS potentiates the paclitaxel-induced apoptosis through enforced caspase 8 activation in H460 cells. Furthermore, the growth suppression effect of TOS/paclitaxel combination on human H460, A549 and H358 NSCLC cell lines were synergistic. Our observations indicate that combination of paclitaxel and TOS may offer a novel therapeutic strategy for improving paclitaxel drug efficacy in NSCLC patient therapy as well as for potentially lowering the toxic side effects of paclitaxel through reduced drug dosage.

Role of p21CIP1 as a determinant of SC-560 response in human HCT116 colon carcinoma cells

SC-560, a strucutral analogue of celecoxib, induces growth inhibition in a wide range of human cancer cells in a cyclooxygenase (COX)-independent manner. Since SC-560 suppresses the growth of cancer cells mainly by inducing cell cycle arrest, we sought to examine the role of p21CIP1, a cell cycle regulator protein, in the cellular response against SC-560 by using p21(+/+)and p21(-/-)isogenic HCT116 colon carcinoma cells. In HCT116 (p21(+/+)) cells, SC-560 dose-dependently induced growth inhibition and cell cycle arrest at the G1 phase without significant apoptosis induction. SC-560-induced cell cycle arrest was accompanied by upregulation of p21CIP1. However, the extent of SC-560-induced accumulation at the G1 phase was approximately equal in the p21(+/+)and the p21(-/-)cells. Nonetheless, the growth inhibition by SC-560 was increased in p21(-/-)cells than p21(+/+)cells. SC-560-induced reactive oxygen species (ROS) generation did not differ between p21(+/+)and p21(-/-)cells but the subsequent activaton of apoptotic caspase cascade was more pronounced in p21(-/-)cells compared with p21(+/+)cells. These results suggest that p21CIP1 blocks the SC-560-induced apoptotic response of HCT116 cells. SC-560 combined with other therapy that can block p21 CIP1 expression or function may contribute to the effective treatment of colon cancer.

Studies on Scintillation Proximity Assay for the mesurement of alpha - hCG / 대한핵의학회잡지

No abstract available.

Comparison of Direct-labeling Method of Antibody with 99mTc and 188Re / 대한핵의학회잡지

PURPOSE: We investigated the direct labeling method of antibody with 99mTc and 188Re and examined the stability and function of these labeled compounds in in vitro and in vivo. MATERIALS AND METHODS: Disulfide bond of nonspecific human IgG was reduced to -SH group by 2-mercaptoethanol. Stannous ion was used to reduce 99mTc and 188Re. The stability of 99mTc-IgG and 188Re-IgG was estimated upto 24 hrs. Biodistribution was evaluated in abscess bearing rats at 4 and 24 hr post-injection of 99mTc or 188Re labeled IgG. RESULTS: The number of -SH group per reduced IgG molecule was 2.34. The labeling yield of 99mTc-IgG and 188Re-IgG were 90% and 95%, respectively. The stability of 99mTc-IgG at 1, 4, 6 and 24 hr was 91%, 83%, 78%, 7% and that of 188Re-IgG, high uptake was found on kidney, blood, stomach and abscess (9.42+/-0.68, 1.43+/-0.24, 0.86+/-0.18, 0.72+/-0.10 %ID/g, respectively). The uptakes at 24 hr were kidney, abscess, stomach, and blood in descending order. In case of 188Re-IgG, high uptake at 4 hr post injection appeared on kidney, blood, abscess and stomach (3.92+/-0.62, 1.32+/-0.08, 0.88+/-0.01, 0.26+/-0.06, respectively). The upatkes at 24 hr were kidney, abscess, blood abd stomach in descending order. The abscess to blood uptake ratio of 99mTc-IgG was 0.5 at 4 hr and 2.02 at 24 hr and that of 188Re-IgG was 0.67 and 1.29. CONCLUSION: 99mTc-IgG and 188Re-IgG and 188Re-IgG canbe labeled efficiently with direct labeling method. However, 99mTc-IgG and 188Re-IgG, labeled with direct method, was unstable. Further study in needed to enhance the stability of the antibody labeling.