Abstract
BackgroundSelective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer’s disease. Interestingly, the expression of this protein is upregulated in several cancers, including primary bladder cancer. However, its role in cancer formation has yet to be discovered. Goniothalamin is a natural product that has been demonstrated to induce apoptosis in various cancer cell lines. In this study, we have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4.MethodsThe cytotoxicity of goniothalamin in human urinary bladder cancer cell line RT4 was assessed using MTT assay and the mode of cell death was determined by Annexin V-FITC/PI labeling assay. Finally, the expression of Seladin-1 protein in goniothalamin-treated RT4 cells was determined by Western blot.ResultsMTT assay showed that the cytotoxicity of goniothalamin on RT4 cells was concentration and time dependent with IC50 values of 61 μM (24 hr), 38 μM (48 hr) and 31 μM for 72 hr, respectively. Cell death induced was confirmed through apoptosis; as assessed using the Annexin V-FITC/PI labeling assay. Furthermore, the involvement of Seladin-1 in goniothalamin-induced apoptosis was evidenced through the cleavage of 60 kDa protein to 40 kDa and 20 kDa. This was followed by a gradual increase of 20 kDa fragment suggesting the involvement of Seladin-1 in goniothalamin-induced apoptosis on RT4 cells.ConclusionThis study demonstrates that goniothalamin induce cytotoxicity and apoptosis on RT4 cells. The involvement of Seladin-1 in goniothalamin-induced apoptosis further suggested that Seladin-1 may play a role in the formation of primary bladder cancer.
Highlights
Selective Alzheimer Disease Indicator-1 is a multifunctional protein first discovered by downregulation of its expression in Alzheimer’s disease
The viability drop from 100% from control and further reduced across concentrations of goniothalamin and time points; with the highest concentration (100 μM) of goniothalamin showed less than 20% of cells were viable following 24 hrs, 48 hrs, and 72 hrs of treatment
Statistical analysis showed that there was a significant reduction in the percentage of cell viability following treatment with goniothalamin at each concentration (i.e., 6.25, 12.5, 25, 50, and 100 μM) compared to control or untreated cells (p < 0.05)
Summary
Selective Alzheimer Disease Indicator-1 (or Seladin-1) is a multifunctional protein first discovered by downregulation of its expression in Alzheimer’s disease. We have elucidated the role of Seladin-1 in goniothalamin-induced cytotoxicity towards human urinary bladder cancer cell line RT4. Selective Alzheimer’s disease Indicator 1 (or Seladin-1) was first discovered in Alzheimer’s disease This gene has an anti-apoptotic function in brain tissue, whereby its downregulation has been associated with neurodegeneration [8]. Seladin-1 was found to be identical to the gene DHCR24, which functions as a key enzyme in cholesterol biosynthesis and lipid raft formation [9,10] It was described as a multifunctional protein. Upon oncogenic induction and oxidative stress, Seladin-1 was found to bind p53 and displace mdm-2 resulted in the accumulation of active p53 This interaction suggests a role of Seladin-1 in the regulation of cell fate [15]. Seladin-1 was demonstrated as lipopolysaccharide (LPS) responsive gene product that regulates anti-inflammatory response [16]
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