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Hong S.-W.,University of Ulsan | Hong S.-W.,Asan Medical Center | Shin J.-S.,University of Ulsan | Shin J.-S.,Asan Medical Center | And 15 more authors.
Cancer Biology and Therapy | Year: 2011

Apoptosis signal-regulating kinase 1 (ASK1) is a key factor for controlling several cellular events including the cell cycle senescence and apoptosis in response to reactive oxygen species (ROS). However the mechanisms that regulate ASK1 protein levels remain largely unexplored. In this study we demonstrate that p34SEI-1 a positive cell cycle regulator with an oncogenic potential inhibits ROS-induced cell death by suppressing ASK1. We first found that p34SEI-1-expressing cells have enhanced resistance to hydrogen peroxide (H2O2). Moreover ectopic expression of p34 SEI-1 clearly inhibited H2O2- induced phosphorylation of ASK1 in the colon cancer cell lines-HCT116 and SW620-in association with a decrease in ASK1 protein levels. Interestingly p34 SEI-1 induced ubiquitination of ASK1 however no direct interaction was found between p34SEI-1 and ASK1. These results suggest that p34SEI-1 inhibits ROS-induced cell death through by indirectly inducing ubiquitination of ASK1. © 2011 Landes Bioscience.

Shin J.-S.,Asan Institute for Life Science | Shin J.-S.,University of Ulsan | Maeng H.-G.,Asan Institute for Life Science | Maeng H.-G.,Seoul National University | And 20 more authors.
Asian Pacific Journal of Cancer Prevention | Year: 2012

Recently, we reported that an ethanol extract of Iris nertschinskia induces p53-dependent apoptosis in the MCF7 human breast cancer cell line. However, the detailed mechanisms were not fully explored. Here, we demonstrate another aspect of the activity of I. nertschinskia in breast cancer cells. We compared the response to an ethanol extract of I. nertschinskia in two different human breast cancer cell lines, Hs578Tand MDA-MB231, respectively with relatively low and high AKT1/2 activity by trypan blue exclusion assay and FACS analysis. Knockdown of endogenous AKT1 or AKT2 in breast cancer cells by RNA interference determined the sensitivity to I. nertschinskia ethanol extract compared to control cells. The I. nertschinskia ethanol extract induced cell death in a manner that depended on the level of phosphorylated AKT1/2 protein and was associated with a significant increase in the sub-G1 cell population, indicative of apoptosis. Our results indicate that an ethanol extract of I. nertschinskia differentially induces cell death in breast cancer cells depending on their level of phosphorylated AKT1/2.

Shin J.-S.,Institute for Innovative Cancer Research | Shin J.-S.,Konkuk University | Hong S.-W.,Institute for Innovative Cancer Research | Lee J.-G.,Seoul National University | And 9 more authors.
International Journal of Molecular Medicine | Year: 2011

Iris nertschinskia, an ornamental plant, is utilized in traditional East Asian medicine for the treatment of skin diseases. However, the biological activity underlying its therapeutic effects remains to be established. In this study, we investigated the anti-tumor effect of the plant extract on MCF7 human breast cancer cells. An ethanol extract of Iris nertschinskia triggered cell death in a dose-dependent manner. Moreover, treatment with the extract promoted p53 phosphorylation in MCF7 cells. Increased phosphorylation of p53, in turn, led to induction of Bax protein, a key regulator of p53-dependent apoptotic cell death, as well as of caspase-7 cleavage in MCF7 cells. Consistently, cells treated with p53-specific siRNA or the caspase inhibitor, Z-VAD, resisted apoptotic cell death induced by the Iris nertschinskia extract. Our results suggest that p53 sensitizes tumor cells to the ethanol extract of Iris nertschinskia by Bax protein induction and caspase-dependent apoptosis.

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