Effect of valproic acid on Expression of Bim gene and viability of ovarian cancer cell line A2780

Background and Objective: Ovarian cancer is the fifth common cancer among women and the number of new cases is increasing. Valproic acid is a histone deacetylase inhibitor effectively used to treat epilepsy and bipolar disease. Recently, this compound has attracted attention as an anti-cancer agent. Bim is one of the most important genes of mitochondrial pathway of apoptosis, and it plays an important role in the biology of cancer. Expression of this gene is greatly reduced in ovarian cancer. This study was done to evaluate the effect of valproic acid on the viability of ovarian cancer cells, apoptosis and Bim gene expression in A2780 line. Methods: In this experimental study, the human ovarian cancer cells (A2780) were grown in RPMI-1640 medium in appropriate culture conditions. The cells were treated by various concentrations valproic acid (1-30 mM) and were incubated for 24, 48 and 72 hours. After the incubation of period, cell viability was investigated using MTT. Apoptosis was analyzed by flow-cytometry method in the cells were treated by valproic acid. The Real time PCR test was used to assess the effect of this drug on the expression of Bim gene. Results: The results of MTT assay showed that valproic acid reduced the viability of A2780 cells, and this effect was time and dose-dependent. The reduction of cell viability at 30 mM concentration and 72 hours after treatment, was maximum and statistically significant (P<0.05). Exposure to valproic acid significantly increased the percentage of apoptotic cells (P<0.05). Also, Valproic acid significantly increased the expression of Bim (P<0.05). Conclusion: Valproic acid reduced viability in ovarian cancer cell line A2780. Valproic acid increased cell death by altering the expression of genes involved in apoptosis in ovarian cancer cell line A2780

Prevalence of the CYP2D6*10&nbsp;(C100T), *4&nbsp;(G1846A), and *14&nbsp;(G1758A) alleles among Iranians of different ethnicities

Ali Bagheri,1 Behnam Kamalidehghan,2 Maryam Haghshenas,3 Parisa Azadfar,4 Leila Akbari,4 Mohammad Hossein Sangtarash,1 Faramarz Vejdandoust,5 Fatemeh Ahmadipour,2 Goh Yong Meng,6 Massoud Houshmand7,8 1Department of Biology, University of Sistan and Baluchestan, Zahedan, Iran; 2Department of Pharmacy, Faculty of Medicine, University of Malaya, Kuala Lumpur, Malaysia; 3Department of Biology, Pardis International Unit, University of Guilan, Rasht, Iran; 4Department of Biology, Science and Research Branch, Azad University, Tehran, Iran; 5Department of Biology, Azad University, Ashkezar Branch, Yazd, Iran; 6Department of Animal Science, Faculty of Veterinary Medicine, Universiti Putra Malaysia, Serdang, Malaysia; 7Medical Genetics Department, Special Medical Center, 8Medical Genetics Department, National Institute for Genetic Engineering and Biotechnology (NIGEB), Tehran, Iran Abstract: The presence of polymorphisms in the&nbsp;CYP2D6&nbsp;gene may modulate enzyme level and activity, thereby affecting individual responses to pharmacological treatment. Here, we compared the prevalence of the CYP2D6*10, *4, and 14* alleles in an Iranian population of different ethnicities with those of other populations. Allele and genotype frequency distributions of CYP2D6*10&nbsp;variants and predicted phenotypes including extensive metabolizers, intermediate metabolizers, and poor metabolizers were analysed in blood samples of 300&nbsp;unrelated healthy individuals in an Iranian population using polymerase chain reaction (PCR)-restriction fragment length polymorphism, PCR-single-strand conformation polymorphism, and direct genomic DNA sequencing. The CYP2D6*4&nbsp;(G1846A) and *14&nbsp;(G1758A) allelic frequencies were not detected in different ethnicities, demonstrating the absence of a significant contribution of these alleles in Iranian populations. However, the T/T, C/T, and C/C genotype frequencies of the CYP2D6*10&nbsp;allele were significantly different (P&lt;0.01) in all Iranian ethnic groups. Additionally, the frequency of the homozygous T/T variant of the CYP2D6*10&nbsp;allele was significantly high in the Lure (P&lt;0.017) and low in the Kurd (P&lt;0.002) ethnicities. The frequency of the T/T variant of the CYP2D6*10&nbsp;allele in central Iran was the highest (P&lt;0.001), while the south of Iran had the lowest frequency (P&lt;0.001). The frequency of the C/T variant of the CYP2D6*10&nbsp;allele was significantly a bit high (P&lt;0.001) in females compare to males, while the frequencies of the T/T variant in females is similar to males, which are 24.4% and 24.3%, respectively. In contrast to absence of the CYP2D6*4&nbsp;(G1846A) and *14&nbsp;(G1758A) alleles in Iranian populations of different ethnicities, the prediction of the CYP2D6*10&nbsp;allele is required in drug research and routine treatment, where the information would be helpful for clinicians to optimize therapy or identify persons at risk of adverse drug reactions before clinical trials. Approximately 39.3% of subjects (24.3% homozygous T/T CYP2D6*10&nbsp;as poor metabolizers and 15% heterozygous C/T CYP2D6*10&nbsp;as intermediate metabolizers) had this allele; therefore, the harmful effects of drugs are relatively common among Iranians. Keywords: pharmacogenetics, polymorphism, cytochrome P450&nbsp;genes, CYP, Iranian population, antipsychotics, antidepressants&nbsp