Zoledronic acid effects interleukin-6 expression in hormone-independent prostate cancer cell lines

OBJECTIVE: To investigate the inhibitory effects of zoledronic acid (ZA) on tumor related growth factor IL-6 in hormone resistant prostate cancer cell lines. The association between apoptosis and IL-6 inhibition was also assessed. MATERIALS AND METHODS: PC-3 and DU145 cell lines were treated with different concentrations of ZA (1-100µM) at various intervals (24-72 h.). The cell viability was investigated by XTT assay and apoptotic effect was evaluated by cell death detection ELISA kit. Caspase 3/7 activity assay was performed to confirm apoptosis. IL-6 levels were measured by ELISA in the supernatant, and these data were also confirmed by IL-6 mRNA analysis using RT-PCR. RESULTS: PC-3 and DU145 cell lines were sensitive to ZA mediated cytotoxicity in a dose- and time-dependent manner. However, the apoptotic effect was significantly different among PC-3 and DU145 cells (p < 0.05). IL-6 secretion was significantly lower in both cell lines, compared to the untreated control cells (p < 0.05). Although the increased inhibition of IL-6 secretion was associated with increased apoptosis in DU145 cells (p = 0.002), there was no similar association for PC-3 cell line (p = 0.347). When compared to the untreated controls, the number of cDNA copies was significantly lower in the ZA treated DU145 cell line at doses of 30 and 90µM (p < 0.05), suggesting a reduced expression of IL-6 mRNA. CONCLUSION: ZA exhibited a time- and dose-dependent apoptotic effect on PC-3 and DU145 prostate cancer cell lines and this effect was associated with inhibited secretion of IL-6 in DU145 cell line

Centro de investigación y observación de aves migratorias para los Pantanos de Villa

Un Centro de Investigación y Observación de Aves Migratorias ubicado en la zona de amortiguamiento de los Pantanos de Villa es un lugar para visitantes e investigadores que tiene como finalidad concientizar a la población de un área que merece ser cuidada y respetada, realzar el valor del entorno natural y recuperar el uso para la conservación del mismo. El énfasis está relacionado al vínculo que debe existir entre la arquitectura y el entorno natural cercano, con espacios que mantengan una relación amigable entre el visitante y la naturaleza, insertándose en el terreno con un bajo impacto ambiental y que ayude a darle mayor valor al área natural, hoy en día olvidada.Tesi

Effects of Thymus serpyllum Extract on Cell Proliferation, Apoptosis and Epigenetic Events in Human Breast Cancer Cells

WOS: 000311457700015PubMed ID: 23163852Thymus (T.) serpyllum (wild thyme) is an aromatic medicinal plant due to its several biological properties, including anticancer activity. Breast cancer is one of the most common malignancies and increasing evidence supports that it is not only a genetic but also an epigenetic disease. Epigenetics investigates changes in gene expression caused by mechanisms that do not involve alterations in DNA sequence. DNA methylation and histone acetylation are the most widely studied epigenetic changes in cancer cells. This study evaluated the effects of T. serpyllum on apoptosis and epigenetic events in breast cancer cells. XTT cell viability assay was used to determine cytotoxicity. DNA fragmentation and caspase 3/7 activity assays were used in the assesment of apoptosis. DNA methyltransferase (DNMT) and histone deacetylase (HDAC) activities were evaluated by ELISA and verified by qRT-PCR. T. serpyllum extract induced significant cytotoxicity in breast cancer cells (MCF-7 and MDA-MB-231) but not in normal cells. It also induced apoptosis and inhibited the DNMT and HDAC activities in MDA-MB-231 cells. In the present study, the first preliminary data on the effects of the methanolic extract of T. serpyllum in normal and breast cancer cells were obtained and suggest that T. serpyllum may be a promising candidate in the development of novel therapeutic drugs for breast cancer treatment.Medical Oncology ClinicsThis research was done at Medical Oncology Research Laboratories, School of Medicine, Tulay Aktas Oncology Hospital, Ege University. We thank Naturin Natural Products Ltd. (Izmir, Turkey) for supplying the plant material (T. serpyllum) and also thank Ruchan Uslu, M.D., who funded this research as the chairman of Medical Oncology Clinics

Targeting Bcl-2 Protein to Enhance Chemosensitivity of Hormone Refractory Prostate Cancer Cell Line, DU-145 by a Synergistic Combination of Docetaxel and Gossypol

WOS: 000296212300016Objective: Docetaxel has become the standard of care for hormone-refractory prostate cancer (HRPC), however drug resistance and toxicity are still challenging in daily cancer practice. The anti-apoptotic pathway centered around the Bcl-2 protein might be one of the responsible pathways. Adding a second drug to docetaxel treatment is one of the most common approaches to solve this problem. Gossypol was reported to have potent anticancer activities in prostate cancer. In this study, we searched for the possible synergistic cytotoxic/apoptotic effects of this combination treatment in hormone- and drug resistant prostate cancer cell line, DU-145 via inhibition of Bcl-2 protein. Material and Methods: XTT cell viability assay was used to assess cytotoxicity of the drugs alone and in combination. For verifying apoptosis, Cell Death Detection Elisa Plus Kit and Caspase-Glo 3/7 assay were used. Western Blot analysis for Bcl-2 protein was carried out. Results: A novel drug combination of docetaxel and gossypol resulted in a significant synergistic cytotoxic activity and apoptosis as compared to any single agent alone, in a dose- and time dependent manner, and also significantly reduced Bcl-2 protein levels in DU-145, in doses that can be used clinically. Condusion: Adding gossypol to docetaxel as a combination treatment in HRPC patients might be a solution for taxane resistant patients. Inhibition of Bcl-2 might be one of the underlying routes of activity for this combination

SYNERGISTIC INHIBITION OF ANGIOGENIN BY COMBINED TREATMENT WITH GOSSYPOL AND CISPLATIN IN A HUMAN OVARIAN CANCER CELL LINE, OVCAR-3

WOS: 00026408950025

High-Resolution Melting Analysis for Screening of Turkish Germline Mutations in BRCA1 and BRCA2

WOS: 000285678300006The germline mutations of breast cancer susceptibility genes 1 (BRCA1) and 2 (BRCA2) are the two most frequently mutated genes in inherited breast and ovarian cancer. Among the most known mutations in these tumor suppressor genes are 5382insC and 185delAG in BRCA1 and 6174delT in BRCA2. The aim of the current study was to investigate the frequency of these BRCA1 and BRCA2 mutations in Western Turkish population. Twenty-five women with a history of self breast cancer and family history, 25 women with a familial history of breast cancer in their first degree-relatives and five healthy women formed the studied groups. DNA from peripheral blood was extracted and analyzed by high-resolution melting (HAM) analysis. None of the 50 patients and five healthy individuals was found to carry 185delAG mutation in BRCA1 and the 6174delT mutation in BRCA2. But, we found the 5382insC mutation in exon 20 of BRCA1 in five patients, having a strong family history. Four of these five patients were from the same family. Our preliminary results indicate that penetrance of 5382insC mutation in BRCA1 mutations is dominant in Turkish population; however, it seems there might be some other genes that contribute more significantly to familial breast carcinoma in Turkish population in BRCA