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  • Title: Synthetic chenodeoxycholic acid derivative HS-1200-induced apoptosis of p815 mastocytoma cells is augmented by co-treatment with lactacystin.
    Author: Seo SY, Jun EJ, Jung SM, Kim KH, Lim YJ, Park BS, Kim JK, Lee S, Suh H, Kim ND, Yoo YH.
    Journal: Anticancer Drugs; 2003 Mar; 14(3):219-25. PubMed ID: 12634616.
    Abstract:
    The antitumor activity of a synthetic chenodeoxycholic acid derivative, HS-1200, on the p815 mastocytoma cell line was investigated. We present several lines of evidence indicating that HS-1200 at 35 microM induced apoptosis of p815 cells. Reduction of mitochondrial membrane potential, the release of cytochrome to cytosol, activation of caspase-3, nuclear condensation, production of poly(ADP-ribose) polymerase cleavage, generation of DNA fragmentation and nuclear condensation were demonstrated. Importantly, HS-1200 inhibited proteasome activity. Next, the combination treatment of HS-1200 or a proteasome inhibitor lactacystin was undertaken. Although the single treatment of 20 microM HS-1200 or 1 microM lactacystin induced apoptosis slightly, the combination treatment of them augmented prominently the extent of apoptosis. The combination therapy of HS-1200 and lactacystin could be potentially a therapeutic strategy reducing the extent and severity of treatment-related toxicity.
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