Oleuropein reduces cisplatin resistance in ovarian cancer by targeting apoptotic pathway regulators.

AIMS: Despite many attempts to treat ovarian cancer, 13,940 individuals perish annually due to this disease worldwide. Chemotherapy is the main approach to ovarian cancer treatment, but the development of drug resistance is a major obstacle to the successful treatment. Oleuropein is a phenolic ingredient with anticancer characteristics. This study was aimed at investigating the effect of oleuropein on cell viability, cisplatin resistance, and apoptosis, as well as the expression levels of miR-34a, miR-125b, miR16, miR-21, and some of their potential target genes in ovarian cancer cells. MAIN METHODS: A2780S and A2780/CP cell lines were exposed to different concentrations of oleuropein alone or in combination with cisplatin for 48 h and 72 h. After that, the cell viability and apoptosis were evaluated using MTT assay and flow cytometry, respectively. Bioinformatics analyses were conducted using STRING database and Cytoscape software. The effect of oleuropein and/or cisplatin on the expression of miRNAs and target genes was assessed via Real-time PCR. KEY FINDINGS: Upon treatment with oleuropein, the expression of P21, P53, and TNFRSF10B increased while that of Bcl-2 and Mcl1 decreased. Moreover, this is the 1st report of a significant decrease in the expression of miR-21 and increase in the expression of miR-34a, miR-125b, and miR16 by oleuropein and/or cisplatin in ovarian cancer cells. SIGNIFICANCE: Altogether, these data revealed that oleuropein regulated the expression of the above-mentioned miRNAs in ovarian cancer cells, which potentially resulted in apoptosis induction, cell proliferation inhibition, and cisplatin resistance decline in ovarian cancer cells. To confirm the results of this study, it is suggested that similar experiments be performed in animal models of ovarian cancer.

The effect of oleuropein on apoptotic pathway regulators in breast cancer cells.

In spite of advancements in breast cancer therapy, this disease is still one of the significant causes of women fatalities globally. Dysregulation of miRNA plays a pivotal role in the initiation and progression of cancer. Therefore, the administration of herbal compounds with anticancer effects through controlling microRNA expression can be considered as a promising therapy for cancer. Oleuropein is the most prevalent phenolic compound in olive. Given its domestic consumption, low cost, and nontoxicity for human beings, oleuropein can be used in combination with the standard chemotherapy drugs. To this end, we examined the effect of oleuropein on two breast cancer cell lines (MCF7 and MDA-MB-231). Our findings revealed that oleuropein significantly decreased cell viability in a dose- and time-dependent manner, while it increased the apoptosis in MCF7 and MDA-MB-231 cells. In the presence of oleuropein, the expression levels of miR-125b, miR-16, miR-34a, p53, p21, and TNFRS10B increased, while that of bcl-2, mcl1, miR-221, miR-29a and miR-21 decreased. The findings pointed out that oeluropein may induce apoptosis via not only increasing the expression of pro-apoptotic genes and tumor suppressor miRNAs, but also decreasing the expression of anti-apoptotic genes and oncomiR. Consequently, oleuropein can be regarded as a suitable herbal medication for cancer therapy.

Association of rs1738074 polymorphism of TAGAP gene with susceptibility to multiple sclerosis in the Iranian population.

Multiple sclerosis (MS) is one of the most common diseases of the central nervous system (CNS) in the Iranian population. To date, association of many genes with the prevalence and progression of the disease have been investigated. In the present study, the impact of rs1738074 single nucleotide polymorphism (SNP) in the TAGAP gene (TAGAP rs1738074) on the risk of MS was evaluated in a sample of the Iranian population. In a case control study, genotyping was performed on 300 patients and normal individuals. The data were analyzed using Pearson's chi-square test. The results showed a significant difference in the SNP frequency between case and control groups (p-value=0.049). The genotype frequencies of TT, TC and CC in patients were 10.67%, 51.33% and 38%, respectively, and in normal individuals were 20.66%, 42.67% and 36.67%, respectively. The results showed a significant difference in the genotype frequency of T/T between the patient and control groups (p<0.05). Interestingly, individuals with T/T genotype were estimated to be less susceptible to MS ((p-value=0.025), Fisher's exact test), odd ratio was 2.18 (controls versus MS patients) with 95% CI: 1.137-4.187. The results suggested that TAGAP rs1738074 polymorphism could be considered as a risk factor in the prevalence of MS in the Iranian population.