Combination of salermide and cholera toxin b induce apoptosis in MCF-7 but not in MRC-5 cell lines

Sirtuin1 is an enzyme that deacetylates histones and several non-histone proteins including P53 during the stress. P300 is a member of the histone acetyl transferase family and enzyme that acetylates histones. Hereby, this study describes the potency combination of Salermide as a Sirtuin1 inhibitor and cholera toxin B [CTB] as a P300 activator to induce apoptosis Michigan Cancer Foundation-7 [MCF-7] and MRC-5. Cells were cultured and treated with a combination of Salermide and CTB respectively at concentrations of 80.56 and 85.43 micro mol/L based on inhibitory concentration 50 indexes at different times. The percentage of apoptotic cells were measured by flow cytometry. Real-time polymerase chain reaction was performed to estimate the messenger ribonucleic acid expression of Sirtuin1 and P300 in cells. Enzyme linked immunosorbent assay and Bradford protein techniques were used to detect the endogenous levels of total and acetylated P53 protein generated in both cell lines. Our findings indicated that the combination of two drugs could effectively induced apoptosis in MCF-7 significantly higher than MRC-5. We showed that expression of Sirtuin1 and P300 was dramatically down-regulated with increasing time by the combination of Salermide and CTB treatment in MCF-7, but not MRC-5. The acetylated and total P53 protein levels were increased more in MCF-7 than MRC-5 with incubated combination of drugs at different times. Combination of CTB and Salermide in 72 h through decreasing expression of Sirtuin1 and P300 genes induced acetylation of P53 protein and consequently showed the most apoptosis in MCF-7 cells, but it could be well-tolerated in MRC-5. Therefore, combination of drugs could be used as an anticancer agent

Association of TP53 gene codon 72 polymorphism with endometriosis risk in Isfahan

Endometriosis is a female health disorder that occurs when cells from the lining of the uterus grow in other areas of the body. The cause of endometriosis is unknown. The purpose of this study was to investigate TP53 gene codon 72 polymorphism in women with endometriosis and compared it with healthy samples in Isfahan. We undertook a case-control study to examine the possible association of the TP53 gene codon 72 polymorphism with the risk of endometriosis in Isfahan. Ninety whole blood specimens from normal people as controls and ninety endometriosis specimens were analyzed. p53 codon 72 genotypes were identified using allele-specific polymerase chain reaction. Frequency of genotype Arg/Arg [Arginine/Arginine] in the samples of endometriosis was 28.9% and in healthy samples 42.2%. Frequency of genotype Pro/Pro [Proline/Proline] in the samples of endometriosis was 15.6% and in healthy ones. Frequency of heterozygote's Arg/Pro was 55.6% in endometriosis samples and 54.45% in healthy ones 3.3%. By comparing statistical genotype Pro/Pro with two other genotypes in both groups there was a statistical meaningful difference between control group and endometriosis group. [p=0.009, CI=95%, OR=5.34 [1047-19.29]]. Recent research shows that genotype Pro/Pro codon72 exon4 TP53 gene may be one predisposing genetic factor for endometriosis in Isfahan