TY - JOUR T1 - Regulation of Cell Proliferation, Gene Expression, Production of Cytokines, and Cell Cycle Progression in Primary Human T Lymphocytes by Piperlactam S Isolated from <em>Piper kadsura</em> JF - Molecular Pharmacology JO - Mol Pharmacol SP - 1057 LP - 1066 DO - 10.1124/mol.58.5.1057 VL - 58 IS - 5 AU - Yuh-Chi Kuo AU - Nai-Shian Yang AU - Cheng-Jen Chou AU - Lie-Chwen Lin AU - Wei-Jern Tsai Y1 - 2000/11/01 UR - http://molpharm.aspetjournals.org/content/58/5/1057.abstract N2 - Effects of piperlactam S (C17H13NO4; mol. wt. 295) isolated from Piper kadsura on phytohemagglutinin (PHA) stimulated cell proliferation were studied in primary culture of human T cells. The results showed that piperlactam S suppressed T cell proliferation at about 0 to 12 h after stimulation with PHA. Synthesis of total cellular proteins and RNA in activated cell cultures was also suppressed. The inhibitory action of piperlactam S was not through direct cytotoxicity. Cell cycle analysis indicated that piperlactam S arrested the cell cycle progression of activated T cells from the G1 transition to the S phase. In an attempt to further localize the point in the cell cycle at which arrest occurred, a set of key regulatory events leading to the G1/S boundary, including gene expression of cytokines and c-Fos protein synthesis, was examined. Piperlactam S suppressed, in activated T lymphocytes, the production and mRNA expression of cytokines such as interleukin-2 (IL-2), IL-4, and interferon-γ in a dose-dependent manner. In addition, Western blot analysis indicated that c-Fos protein expressed in activated T lymphocytes was decreased by piperlactam S. Results of kinetic study indicated that inhibitory effects of piperlactam S on IL-2 mRNA expressed in T cells might be related to blocking c-Fos protein synthesis. Thus, the suppressant effects of piperlactam S on proliferation of T cells activated by PHA seemed to be mediated, at least in part, through inhibition of early transcripts of T cells, especially those of important cytokines, IL-2, IL-4, and arresting cell cycle progression in the cells. ER -