caa a22 4500 463186303 CHVBK 20180406164854.0 cr unu---uuuuu 170326e20070901xx s 000 0 eng 10.1007/s00726-006-0437-4 doi (NATIONALLICENCE)springer-10.1007/s00726-006-0437-4 Cellular thiol status-dependent inhibition of tumor cell growth via modulation of p27kip1 translocation and retinoblastoma protein phosphorylation by 1′-acetoxychavicol acetate [Elektronische Daten] [Y. Unahara, A. Kojima-Yuasa, M. Higashida, D. O. Kennedy, A. Murakami, H. Ohigashi, I. Matsui-Yuasa] Summary.: 1′-Acetoxychavicol acetate (ACA) has been shown to inhibit tumor cell growth, but there is limited information on its effects on cell signaling and the cell cycle control pathway. In this study, we sought to determine how ACA alters cell cycle and its related control factors in its growth inhibitory effect in Ehrlich ascites tumor cells (EATC). ACA caused an accumulation of cells in the G1 phase and an inhibition of DNA synthesis, which were reversed by supplementation with N-acetylcysteine (NAC) or glutathione ethyl ester (GEE). Furthermore, ACA decreased hyperphosphorylated Rb levels and increased hypophosphorylated Rb levels. NAC and GEE also abolished the decease in Rb phosphorylation by ACA. As Rb phosphorylation is regulated by G1 cyclin dependent kinase and CDK inhibitor p27kip1, which is an important regulator of the mammalian cell cycle, we estimated the amount of p27kip1 levels by western blotting. Treatment with ACA had virtually no effect on the amount of p27kip1 levels, but caused a decrease in phosphorylated p27kip1 and an increase in unphosphorylated p27kip1 as well as an increase in the nuclear localization of p27kip1. These events were abolished in the presence of NAC or GEE. These results suggest that in EATC, cell growth inhibition elicited by ACA involves decreases in Rb and p27kip1 phosphorylation and an increase in nuclear localization of p27kip1, and these events are dependent on the cellular thiol status. Springer-Verlag, 2006 Keywords: ACA - Tumor cell growth - Rb - p27kip1 - Glutathione - Cell cycle nationallicence pRb : hyperphosphorylated Retinoblastoma gene product nationallicence Rb : hypophosphorylated Rb nationallicence p27kip1 : CDK inhibitor p27kip1 nationallicence EATC : Ehrlich ascites tumor cells nationallicence NAC : N-acetylcysteine nationallicence GEE : glutathione ethyl ester nationallicence Unahara Y. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut Kojima-Yuasa A. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut Higashida M. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut Kennedy D. O. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA aut Murakami A. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan aut Ohigashi H. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan aut Matsui-Yuasa I. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut Amino Acids Springer-Verlag 33/3(2007-09-01), 469-476 0939-4451 33:3<469 2007 33 726 https://doi.org/10.1007/s00726-006-0437-4 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00726-006-0437-4 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Unahara Y. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Kojima-Yuasa A. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Higashida M. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut NATIONALLICENCE 700 1- Kennedy D. O. Department of Environmental Health Sciences, Mailman School of Public Health, Columbia University, New York, NY, USA aut NATIONALLICENCE 700 1- Murakami A. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Ohigashi H. Division of Applied Life Sciences, Graduate School of Agriculture, Kyoto University, Kyoto, Japan aut NATIONALLICENCE 700 1- Matsui-Yuasa I. Department of Food and Human Health Sciences, Graduate School of Human Life Science, Osaka City University, Osaka, Japan aut NATIONALLICENCE 773 0- Amino Acids Springer-Verlag 33/3(2007-09-01), 469-476 0939-4451 33:3<469 2007 33 726 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer