[17] described that

activity of IDH1 is coordinately regulated with the cholesterol and fatty acid biosynthetic pathways, suggesting that IDH1 provides NADPH required by these pathways. It was described IDH1 appears to function as a tumor suppressor that, when mutationally inactivated, contributes to tumorigenesis [22]. IDH1 is likely to function as a tumor suppressor gene rather than as an oncogene [22]. IDH1, encoding two TCA enzymes, fumarate hydratase (FH) and succinate dehydrogenase (SDH), has been found to sustain loss-of-function mutations in certain human tumors, which likewise contribute to tumor growth via stimulating the HIF-1a pathway and mutationally altering metabolic enzymes [33, buy Rapamycin 34]. As IDH1 also catalyzes the production of NADPH, it is possible that a decrease in NADPH levels resulting from IDH1 mutation contributes to tumorigenesis through effects on cell metabolism and growth [17]. Zhao et al. [22] showed that mutation of IDH1 impairs the enzyme’s affinity for its substrate and dominantly inhibits CFTR modulator wild type IDH1 activity with the formation of catalytically inactive heterodimers. Mutation of the IDH1 gene was strongly

correlated with a normal cytogenetic status [21]. In this study, we firstly demonstrate that IDH1 is detected in U2OS with wild type p53 and MG63 with mutation p53 by immnohistochemistry, Realtime-PCR and Western Blotting. Intriguingly, our study demonstrates that IDH1 markedly increases in U2OS compare with MG63 triclocarban not only in mRNA level but also in protein level. It is conceivable that the expression of IDH1 may relate to p53. Human osteosarcoma cell line MG63 was found with Deletion and rearrangement of the p53 gene [35–37]. No Wild type p53 expression could be detected in this cell line. Our results are in accordance with the results of Masuda et al. [6] and Mulligan et al. [36] and indicate that inactivation of p53

is a common event in osteosarcoma development. In addition, we authenticate the wild type p53 in human osteosarcoma cell line U2OS in our study. P53 is described as a tumor suppressor in many tumors. Culotta and Koshland [38] and Harris et al [39] gave an extensive account of its discovery and function as well as the use of p53 in cancer risk assessment. Activity of p53 ubiquitously lost in osteosarcoma either by mutation of the p53 gene itself or by loss of cell signaling upstream or downstream of p53 [40]. Xue et al. [41] reported that p53 inactive may be required for maintenance of aggressive tumors. Marion et al. [42] showed that p53 is critical in preventing the generation of human pluripotent cells from suboptimal parental cells. Harris and Hollstein [39] highlighted the clinical implications of changes in the p53 gene in the pathogenesis, diagnosis, prognosis, and therapy of human cancer. But, little is known about the combinatory role of p53 and IDH1 in OS cells. We are curious about the role of p53 and IDH1 in osteosarcoma.