At first the APC is a kDa protein

At first, the APC is a 310kDa protein divided into three domains such as N-terminal, central core and C-terminal domain [102], plays a major role to regulate the Wnt signaling pathway in human cancer by translating β-catenin from the Oxonic acid potassium salt to the nucleus [103]. The SIRT1 regulates the Wnt signaling pathway by activating and colocalizing with dsh protein in the cytoplasm. It is physically associated with DNMT1 (DNA Methyltransferase 1), is an enzyme responsible for DNA methylation and it is enhanced activity is regulated by SIRT1 [104]. However, due to the enhanced activity or high expression of DNMT1 promotes DNA hypermethylation of the CpG island promoter in APC resulting silencing of tumor suppressor function (Fig. 6) [105]. In cancer cell progression, GSK3β and SIRT1 have a relationship where the substrate of SIRT1 and PI3 (phosphatidylinositol 3-kinase) has been activated by Akt, an upstream regulatory kinase of GSK3β [106]. Those Akt have deacetylated via SIRT1 and triggers the phosphorylation of GSK3β at ser9 residue to inhibit the GSK3β activity (Fig. 7) [107]. But when it activates, it abolishes the effect of SIRT1 functions [108], [109]. While the activation of Wnt signaling pathway, the Dsh protein inhibits the phosphorylation of β-catenin by disrupting the destruction complex. However, the unphosphorylated β-catenin acetylated through K345 and CBP at k49 residue, resulting nuclear accumulation of β-catenin leads to upregulation of TCF/LEF (T-cell factor/Lymphoid enhancer factor) transcription factors [110], [111]. Flowingly, the acetylated β-catenin has been translated into the nucleus where it can bind to the acetylated LEF1 (Fig. 8). Further, the binding of LEF1 lysine residue and SIRT1 in nucleus deacetylate at histone to regulate the transcription activation of downstream target genes [112], [113].
Drugs reported to target the aurora kinases The development of cancer is the outcome of overexpression or deregulation of Aurora kinases. Hence, the inhibition of these kinases might be an effective anticancer strategy [130]. Nowadays, there are many small molecule drug inhibitors are available to target Aurora kinases, which all are under clinical development [131]. Here, some of the most advanced inhibitors are briefly discussed under the classification of Pan-Aurora inhibitors, Aurora A inhibitors and Aurora B inhibitors (Table 2).
Conclusion
Conflict of interest
Introduction Aurora kinases function mainly during mitosis and three types were identified in mammals, all are crucial during mitosis for centromere maturation. A new approach in inhibiting cancer growth that shows great promise for structure-based drug development is targeting enzymes central to cellular mitosis [1]. Aurora kinases, so named because the scattered mitotic spindles generated by mutant forms resemble the Aurora Borealis, have gained a great deal of attention as possible anticancer drug targets [2]. Oxidative stress is an indicator for the innumerable pathophysiological manifestations like cancer, ageing, neurodegenerative diseases [3]. The proper segregation of chromosomes is important for genetic stability during embryonic development. Improper and incomplete binding of microtubules to kinetochores may lead to chromosome miss-segregation resulting in apoptosis or aneuploidy [4]. Mitotic checkpoint complex helps in control of all these errors, which operates the spindle assemble check point pathway in eukaryotic cells. Aurora kinase malfunction correlates with development of cancer, commonly due to defects in mitosis induced by altered expression of aurora kinases which acts as checkpoints of SAC function, chromosomes alignment and cytokinesis. Thus, the studies about these aurora kinase mechanism and generation of specific kinase inhibitors play a key role in cancer research. Besides mitotic role of aurora kinases has been reported during maturation of oocytes in mouse [5]. Based on the above studies the current work is carried out in zebrafish embryos to assess the food colour induced growth retardation and its protection. Zebrafish embryogenesis is external and ex-uterus does not interfere with maternal transcripts, and thus early embryonic lethality may be avoided [6].