Cancer stemness kinase inhibitor amcasertib: a promising therapeutic agent in ovarian cancer stem and cancer cell models with different genetic profiles.

Ovarian cancer, often referred to as the 'silent killer,' is a significant contributor to mortality rates. Emerging evidence implicates Nanog as a potential therapeutic target in ovarian cancer. Amcasertib (BBI-503) is an orally administered primary class stemness kinase inhibitor that effectively targets NANOG and various cancer stem cell pathways by specifically inhibiting serine-threonine stemness kinases. This study aimed to evaluate the antineoplastic effects of Nanog inhibition, a critical transcription factor associated with pluripotency and its role in ovarian cancer tumorigenesis, using the novel therapeutic agent Amcasertib in ovarian cancer cells characterized by distinct genetic profiles. The cytotoxicity of Amcasertib was assessed in both ovarian cancer and cancer stem cell models utilizing the Xelligence-RTCA system. The impact of the determined IC50 dose on apoptosis, invasion, migration, epithelial-mesenchymal transition (EMT), cell cycle progression, colony formation, and spheroid growth was evaluated using appropriate analytical techniques. Our findings revealed that Amcasertib exhibited significant antiproliferative effects and induced apoptosis in ovarian cancer and cancer stem cells. Moreover, Amcasertib caused G1 phase arrest and impeded colony formation in MDAH-2774 cells. Additionally, Amcasertib effectively inhibited spheroid growth in OVCAR-3 and OCSC cells. Notably, it demonstrated the ability to suppress invasion and migration in MDAH-2774 and OCSC cells. Furthermore, the suppression of Nanog-mediated stem cell-like features by Amcasertib was particularly pronounced in ER-negative ovarian cancer and cancer stem cells, highlighting its high anticancer efficacy in this subgroup. These results suggest that Amcasertib holds promise as a potential standalone or combination therapy agent for the treatment of ER-negative ovarian cancer.

A Study Investigating the Role of 2 Candidate SNPs in Bax and Bcl-2 Genes in Alzheimer's Disease.

OBJECTIVE: The proto-oncogene Bax (Bcl-2-associated X protein) and related protein Bcl-2 (B-cell chronic lymphocytic leukemia/lymphoma-2) genes are triggers of apoptosis in Alzheimer's disease (AD). The balance of these proteins has an important role in the death or life of a neuronal cell, and the functional polymorphisms in genes expressing these proteins have been found to promote apoptosis. To investigate the role of Bax and Bcl-2 genes in AD, we examined the presence of the 2 polymorphisms in peripheral blood. To our knowledge, this is the first clinical association study of these 2 functional SNPs using the peripheral blood of patients with AD. METHODS: Bax (rs4645878) and Bcl-2 (rs2279115) in Alzheimer's patients (N = 132) and healthy controls (N = 109), aged 65 to 85 years, were analyzed by qPCR (Quantitative Polymerase Chain Reaction) using TaqMan probe technology. Statistical analyses were done using SPSS, 11.5. The differences between groups were analyzed using an independent-samples t test. The relationships between genotypes and alleles were analyzed using chi-square or likelihood ratio test. The Hardy-Weinberg balance was checked for the patient and control groups. A p-value of less than 0.05 was taken as significant. RESULTS: Sporadic AD patients and non-demented age matched control subjects were genotyped in this case-control study. No statistically significant relationship was found between the patients and controls for allele or genotype frequencies (p>0.05). CONCLUSION: Our data suggest that these two polymorphisms do not contribute to AD in the population from the Mersin region of the Eastern Mediterranean. Further studies with larger sample sizes must be conducted to ascertain the association between the 2 polymorphisms.