Hsp Inhibitor is Affective Against Adenocarcinomic Human Alveolar Basal Epithelial Cells Through Modulating ERK/MAPK Signaling Pathway.

The extracellular signal-regulated kinase (ERK) - mitogen-activated protein kinase (MAPK) pathway regulates cell proliferation, differentiation, and apoptosis. Heat Shock Protein 90 (HSP90) is required to activate proto-oncogenic protein kinases and promotes tumor growth through anti-apoptotic effects on A549-non-small cell lung cancer (NSCLC). Therefore, deregulation of the ERK-MAPK pathway and abnormal expression of HSP90 are reasonably frequent events in NSCLC. In this study, novel perimidine-pyrazole compounds employed to block ERK-MAPK deregulation through inhibiting HSP dependent cancer cell survival mechanisms. A set of perimidine-pyrazole derivatives effects was monitored on NSCLC cell line. Array experiments performed to understand the effect of the compounds on signaling pathways and results were analyzed by gene enrichment analysis. Further, senescence and apoptosis experiments were performed to support the enrichment results along with in silico methods to determine perimidine-pyrazole/HSP interactions. Treatment of NSCLC cells with perimidine-pyrazole derivatives displayed cancer-inhibitory, pro-senescent and pro-apoptotic effects on NSCLC cells through ERK/MAPK pathway and these compounds are promising templates for designing anticancer drugs.

Mesenchymal Stem Cells Combined With IFNγ Induce Apoptosis of Breast Cancer Cells Partially Through TRAIL.

BACKGROUND: Mesenchymal stem cells (MSCs) have gained remarkable attention because of their ability to dualistically regulate tumor growth. The main objective of this study was to evaluate the apoptotic effects of human bone marrow-derived (hBM) MSCs in combination with interferon gamma (IFN-γ) on MCF-7 breast cancer cells, and to determine the cytokines involved in the apoptotic process. MATERIALS AND METHODS: hBM-MSCs were co-cultured with MCF-7 cells either directly and indirectly for 72 h in-vitro. Levels of tumor necrosis factor-related apoptosis-inducing ligand (TRAIL), apoptosis and cytokines were analyzed. RESULTS: hBM-MSCs increased the apoptosis of MCF-7 cells partially through TRAIL in vitro. IFN-γ enhanced the apoptotic effect of hBM-MSCs (p<0.001). CONCLUSION: hBM-MSCs in combination with IFN-γ might be a suitable therapy for breast cancer.

Silver nanoparticle/capecitabine for breast cancer cell treatment.

This study aimed to evaluate antiproliferative and proapoptotic effects of Capecitabine bonded silver particles on human breast cancer cells (MCF-7). Different sizes of Ag NPs (in sizes 5, 10, 15, 30 nm) were synthesized. The characterization of silver and drug-bonded silver nanoparticles was performed through UV-VIS, FTIR, and SEM analysis. Silver and drug-bonded silver nanoparticles were measured by zetasizer. Antiproliferative and proapoptotic effects of capecitabine, silver and drug-bonded silver nanoparticles were evaluated using XTT, Anneksin V, respectively. According to the results, silver nanoparticles of 10 nm size have shown the lowest toxic effect. Drug-bonded nanoparticles significantly increased the number of early and late apoptotic cells on MCF-7 cells.

Distribution and Effects of CDKN2 p16 540 C>G and 580 C>T, and MDM2 SNP309 T>G Polymorphisms in Patients with Primary Brain Tumors.

BACKGROUND/AIM: Primary brain tumors are unique tumors due to their different pathobiological behavior, while they rarely metastasize outside the central nervous system. Regarding the oncogenesis of primary brain tumors, it was shown that changes in functions of p16 and mouse double minute 2 homolog (MDM2) are related to tumor pathogenesis by enhancing cell proliferation and malign development. The present study aims to evaluate the possible associations between cyclin-dependent kinase 2 (CDKN2) p16 540 C>G and 580 C>T, MDM2 single nucleotide polymorphism 309 (SNP309) T>G polymorphisms and primary brain tumor. MATERIALS AND METHODS: Using polymerase chain reaction-restriction fragment length polymorphism technique, we determined SNPs in 67 patients with primary brain tumors and 71 healthy volunteers without malignancy. RESULTS: The frequency of CC genotype for CDKN2 p16 540 C>G was significantly two-fold higher (p<0.001) and possessing a C allele conferred a ~7-fold increased risk (p=0.005) of primary brain tumor. We also found that the CC genotype produced a higher ~4-fold risk of glioma (p=0.001) and the G allele had a possibly protective role against meningioma (~4.8-fold reduced risk, p=0.001). We found no significant associations for CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants between cases and controls. CGT haplotype was significantly less frequent in patients with primary brain tumors and glioma cases (p=0.009 and p=0.028, respectively) than controls. CGG haplotype was significantly less frequent in patients with meningioma versus the control group (p=0.023). CONCLUSION: These findings show that CDKN2 p16 540 C>G, CDKN2 p16 580 C>T and MDM2 SNP309 T>G variants and their haplotypes may be risk factors for the development of primary brain tumors, especially of glioma.