TY - JOUR AB - Vitamin C is considered as an important anticancer therapeutic agent although this view is debatable. In this study, we introduce a physiological mechanism demonstrating how vitamin C exerts anticancer activity that induces cell cycle arrest and apoptosis. Our previous and current data reveal that p53 tumor suppressor is the prerequisite factor for stronger anticancer effects of vitamin C. In addition, vitamin C-mediated cancer cell cytotoxicity appears to be achieved at least partly through the downregulation of the p34SEI-1 oncoprotein. Our previous study showed that p34SEI-1 increases the survival of various types of cancer cells by inhibiting their apoptosis. Present data suggest that vitamin C treatment decreases the p34SEI-1 expression at the protein level and therefore alleviates its anti-apoptotic activity. Of note, SIAH1, E3 ubiquitin ligase, appears to be responsible for the p34SEI-1 polyubiquitination and its subsequent degradation, which is dependent on p53. In summary, vitamin C increases cancer cell death by inducing SIAH1-mediated polyubiquitination/degradation of the p34SEI-1 oncoprotein in a p53-dependent manner. AD - Department of Life Systems, Sookmyung Women's University, Seoul 140-742, Republic of Korea AU - Lee,Soonduck AU - Kim,Jinsun AU - Jung,Samil AU - Li,Chengping AU - Yang,Young AU - Kim,Keun,Il AU - Lim,Jong-Seok AU - Kim,Yonghwan AU - Cheon,Choong-Il AU - Lee,Myeong-Sok DA - 2015/03/01 DO - 10.3892/ijo.2015.2840 EP - 1384 IS - 3 JO - Int J Oncol KW - vitamin C p53 p34SEI-1 SIAH1 PY - 2015 SN - 1019-6439 1791-2423 SP - 1377 ST - SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity T2 - International Journal of Oncology TI - SIAH1-induced p34SEI-1 polyubiquitination/degradation mediates p53 preferential vitamin C cytotoxicity UR - https://doi.org/10.3892/ijo.2015.2840 VL - 46 ER -