Serap Ozer Yaman

Antiproliferative and proapoptotic activity of Turkish propolis on human lung cancer cell line

abstract Cancer is a heterogeneous disease, two of whose characteristic features are uncontrollable cell proliferation and insufficient apoptosis. Various studies have investigated the antiproliferative effects of propolis, a natural bee product, from different countries, and its cytotoxic effects have been attributed to its polyphenol contents. The purpose of this study was to show the cytotoxic effects, and possible mechanisms involved, of ethanolic extract of Turkish propolis (EEP) on the human lung cancer (A549) cell line. Cytotoxic activity of EEP on A549 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic action of EEP on A549 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, endoplasmic reticulum stress using RT-PCR, and caspase activity using luminometric analysis. EEP exhibited selective toxicity against A549 cells compared to normal fibroblast cells. We determined that EEP arrested the cell cycle of A549 cells at the G1 phase, induced endoplasmic reticulum stress, caspase activity, and apoptosis and reduced mitochondrial membrane potential. These results indicate that Turkish propolis is capable of reducing cancer cell proliferation and may have a promising role to play in the development of new anticancer drugs in the future.

Investigation of the expression of irisin and some cachectic factors in mice with experimentally induced gastric cancer

BACKGROUND The purpose of this study was to determine whether irisin is secreted by gastric tumor cells experimentally induced in mice, and also if it has any effect on cancer cachexia. DESIGN AND METHODS 12 out of 60 BALB/c mice were used as a control group, while N-nitroso-N-methylurea (MNU) was administered orally to the remaining 48. After 150 days, the surviving mice were sacrificed by decapitation, blood and stomach, skeletal muscle, brown and white adipose tissue specimens were collected. Following histopathological evaluation of the stomach tissues, it was decided to create four groups, one control group and three consisting of mice administered MNU, no cancer, pre-cancer and cancer. Gene expression analyses of fibronectin type III domain containing protein 5 (FNDC5) and some cachexia-related proteins were performed in tissue samples, while levels of irisin, and various inflammatory and tumor markers together with cachectic factors were determined in serum samples. RESULTS The levels of inflammatory, tumor markers and cachectic factors in serum samples were significantly higher in the cancer group compared with the control group. No expression of FNDC5 or zinc-α-2 glycoprotein, a cachectic factor, was observed in gastric tissues from the control and MNU groups, whereas significantly increased FNDC5 expression was determined in the both white and brown adipose tissues from the cancer group. CONCLUSION Increased FNDC5 expression in white and brown adipose tissues may have a cachectic effect in mice with induced cancer. However, it is not possible to explain the mechanism of the relationship between irisin and gastric cancer development on the basis of the results of this study.

Morus Rubra Extract Induces Cell Cycle Arrest and Apoptosis in Human Colon Cancer Cells Through Endoplasmic Reticulum Stress and Telomerase.

ABSTRACT Many studies have reported cytotoxic effects of different Morus species, but there have been only limited studies on the cytotoxic effect of Morus rubra. The aims of this study were to evaluate the cytotoxic effect of dimethyl sulfoxide extract of M. rubra and to investigate, for the first time, its probable cytotoxic activity in human colon cancer (WiDr) cells, together with the mechanism involved. The cytotoxic activity of extract was determined using MTT assay. The mechanism involved in the cytotoxic effect of extract was then evaluated in terms of apoptosis, and the cell cycle using flow cytometry, mitochondrial membrane potential (MMP) was investigated using the fluorometric method, and expression levels of telomerase and C/EBP homologous protein (CHOP) were investigated using reverse-transcription PCR (RT-PCR). M. rubra extract exhibited moderate selective cytotoxicity on colon cancer cells compared with fibroblast cells. Extract induced cell cycle arrest at the G1 phase and apoptosis via reduced MMP in WiDr cells. Additionally, M. rubra extract significantly repressed telomerase and induced CHOP expressions in WiDr cells. Our results demonstrate that targeting telomerase and endoplasmic reticulum stress represents a promising strategy in colon cancer therapy, and M. rubra may have considerable potential for development as a novel natural product-based anticancer agent.

Antiproliferative and apoptotic effect of Morus nigra extract on human prostate cancer cells

Background: Morus nigra L. belongs to the family Moraceae and is frequently used in traditional medicine. Numerous studies have investigated the antiproliferative effects of various extracts of different Morus species, but studies involving the in vitro cytotoxic effect of M. nigra extract are very limited. The purpose of this study was to evaluate the phenolic composition and antioxidant activity of dimethyl sulfoxide extract of M. nigra (DEM) and to investigate, for the first time, the probable cytotoxic effect in human prostate adenocarcinoma (PC-3) cells together with the mechanism involved. Methods: Total polyphenolic contents (TPC), ferric reducing antioxidant power (FRAP) and phenolic compounds of DEM were evaluated using spectrophotometric procedures and HPLC. The cytotoxic effect of DEM on PC-3 cells was revealed using the MTT assay. Mechanisms involved in the cytotoxic effect of DEM on PC-3 cells were then investigated in terms of apoptosis, mitochondrial membrane potential and cell cycle using flow cytometry, while caspase activity was investigated using luminometric analysis. Results: TPC and FRAP values were 20.7 ± 0.3 mg gallic acid equivalents and 48.8 ± 1.6 mg trolox equivalents per g sample, respectively. Ascorbic acid and chlorogenic acid were the major phenolic compounds detected at HPLC analysis. DEM arrested the cell cycle of PC-3 cells at the G1 phase, induced apoptosis via increased caspase activity and reduced mitochondrial membrane potential. Conclusions: Our results indicate that M. nigra may be a novel candidate for the development of new natural product based therapeutic agents against prostate cancer.

Status of vitamin D, antioxidant enzymes, and antioxidant substances in neonates with neonatal hypoxic-ischemic encephalopathy

Abstract Objective: To investigate the concentration of vitamin D (VD), glutathione peroxidase (GP), superoxide dismutase (SOD), malondialdehyde (MDA), and advanced oxidation protein products (AOPP) in neonates with hypoxic-ischemic encephalopathy (HIE). Material and methods: This study was performed prospectively in term neonates treated for HIE. Samples were collected from the neonates in study and control groups at 6–14 h and on day 5 of their lives for 25-OH vitaminD3, antioxidant enzymes including GP and SOD and oxidants substances including MDA and AOPP. Results: This study was performed with 31 term neonates with HIE and 30 healthy term neonates. Maternal VD level was statistically lower in the study group (9.8±6.8 ng/mL) than the control (16.4±8.7 ng/mL) (p = 0.002). SOD and MDA levels were significantly high, and VD level was significantly low in the study group on the first day of life (p = 0.001 and p = 0.028, respectively). SOD and GP levels were significantly high in the study group on day 5 (p < 0.05). VD was significantly low in the study group on day 5 and the proportion of subjects with VD below 5 ng/ml was significantly lower in the control group (p = <0.05). Conclusion: VD has neuroprotective and antioxidant properties. We detected VD levels were low in infants with HIE and their mothers. This finding may be useful for decreasing of brain damage.

Detection of autoantibodies against carbonic anhydrase I and II in the plasma of patients with gastric cancer

Cancer is the second leading cause of death and gastric cancer is the fourth most common cancer type worldwide. Investigation of autoantibodies in cancer patients has been a popular research area in recent years. The aim of the current study was to investigate carbonic anhydrase I and II (CA I and II) autoantibodies in the plasma of subjects with gastric cancer based on the information and considerations of autoimmune relation of gastric cancer. Anti-CA I and II antibody levels were investigated by ELISA in plasma samples of fifty two patients with gastric cancer and thirty five healthy peers. Anti-CA I and II antibody titers of the gastric cancer group were significantly higher compared with the control group (p = 0.004, p = 0.0001, respectively). Plasma anti-CA I levels of the metastatic group were lower than the non-metastatic group and this difference was found statistically significant (p < 0.05), but there was no statistical difference between plasma anti-CA II levels of the groups. CA I and II autoantibody titers in patients with gastric cancer were found higher compared to healthy subjects and the results suggest that these autoantibodies may be involved in the pathogenesis of gastric cancer.

Autoantibodies against Carbonic Anhydrase I and II in Patients with Acute Myeloid Leukemia

Objective: Cancer, one of the principal causes of death, is a global social health problem. Autoantibodies developed against the organism’s self-antigens are detected in the sera of subjects with cancer. In recent years carbonic anhydrase (CA) I and II autoantibodies have been shown in some autoimmune diseases and carcinomas, but the mechanisms underlying this immune response have not yet been explained. The aim of this study was to evaluate CA I and II autoantibodies in patients with acute myeloid leukemia (AML) and to provide a novel perspective regarding the autoimmune basis of the disease. Materials and Methods: Anti-CA I and II antibody levels were investigated using ELISA in serum samples from 30 patients with AML and 30 healthy peers. Results: Anti-CA I and II antibody titers in the AML group were significantly higher compared with the control group (p=0.0001 and 0.018, respectively). A strong positive correlation was also determined between titers of anti-CA I and II antibodies (r=0.613, p=0.0001). Conclusion: Our results suggest that these autoantibodies may be involved in the pathogenesis of AML. More extensive studies are now needed to reveal the entire mechanism.

Effects of 900-MHz electromagnetic fields exposure throughout middle/late adolescence on the kidney morphology and biochemistry of the female rat

The effect of the electromagnetic field (EMF) established when cell phones are in use on human health, and particularly the head, has been the subject of major scientific research. Phones are usually carried near the lumbar region when not in use, and the kidneys will also inevitably be affected by such fields. We investigated the effects on the kidneys of female rats exposed to a continuous 900-megahertz (MHz) EMF for 1 h daily in mid-late adolescence. Control, sham, and EMF groups were established. The EMF was applied to the application group rats daily on postnatal days 35–59. A pseudo-megahertz effect was applied to sham group rats. All animals were euthanized on postnatal day 60. Right kidney tissues were subjected to routine procedures. Malondialdehyde, total antioxidant status, and total oxidant status (TOS) were investigated in left kidneys, and the oxidative stress index (OSI) was also calculated from these. Histopathological analysis revealed no pathology in either the control or sham groups. However, findings including hemorrhage in glomerulus, vacuolization and irregularity in the proximal and distal tubular epithelium, diffuse glomerular degeneration and edema, occasional degeneration in Bowman capsules, hemorrhage in the medullary region, disturbed nucleus location and morphology, and tubular edema in the cortex were observed in the EMF groups. TOS and OSI values were lower in the EMF group (9.4316 ± 1.0211 and 0.8461 ± 0.0826, respectively) and the sham group (8.2171 ± 0.6437 and 0.7358 ± 0.0545, respectively) than in the control group (11.1522 ± 1.3389 and 1.0085 ± 0.1174, respectively) (p < 0.05). In conclusion, exposure to a continuous 900-MHz EMF for 1 h daily during middle and late adolescence may cause various changes in the female rat kidney at postnatal day 60.

Primula vulgaris extract induces cell cycle arrest and apoptosis in human cervix cancer cells

Primula vulgaris belongs to the genus Primula, members of which are frequently used in folk medicine. Various studies have investigated the cytotoxic effect of different Primula species, but there have been limited studies on the cytotoxic effect of P. vulgaris. The aim of this study was to investigate the cytotoxic effects, and possible mechanisms involved, of P. vulgaris flower extract on human cervical cancer (HeLa) cells. The cytotoxic effect of the extract on HeLa cells was revealed using the MTT assay. Mechanisms involved in the extracts cytotoxic effect were then investigated in terms of apoptosis, mitochondrial membrane potential, and the cell cycle, using fluorometric methods. P. vulgaris flower extract exhibited selective cytotoxic effects against HeLa cells by arresting their cell cycle at the S phase, and inducing the number of apoptotic cells compared to normal fibroblast cells by reducing mitochondrial membrane potential in a concentration-dependent manner. This is the first study to reveal the antiproliferative effect of P. vulgaris flower extract. Further studies are now needed to identify the cytotoxic molecules in the extract and their mechanisms.

The clinical importance of serum urokinase plasminogen activator receptor and carbonic anhydrase IX levels and the effect of anthracycline-based adjuvant chemotherapy on these biomarkers in breast cancer

Introduction: Breast cancer mortality rates after metastasis is high. Urokinase plasminogen activator receptor (uPAR) and carbonic anhydrase IX (CAIX) play very important roles during tumor cell invasion and metastasis. The purpose of this study was to evaluate plasma levels of uPAR and CAIX and the effect of anthracycline-based chemotherapy on these biomarkers in patients with operable breast cancer. Materials and Methods: Sixty-five patients and 25 age-matched healthy controls were enrolled. Levels of uPAR and CAIX were investigated before and after adjuvant chemotherapy. Basal (prechemotherapy) uPAR and CAIX levels in patients were compared with those in healthy controls and in patients after 3 cycles of chemotherapy. Levels of uPAR and CAIX were determined using the ELISA method. Results: uPAR and CAIX levels were significantly higher in patients (P: 0.02 and P: 0.03, respectively). Postchemotherapy uPAR and CAIX levels were higher than basal levels (P: 0.645 and P < 0.001, respectively). A cut-off value of 27.99 pg/mL for uPAR was associated with 45.31% sensitivity and 84.62% specificity, and with a positive predictive value (PPV) of 87.9% and a negative predictive value (NPV) of 38.6%. A cut-off value of 777.84 pg/mL for CAIX was associated with 90.62% sensitivity and 30.77% specificity, and with a PPV of 76.3% and an NPV of 57.1%. Conclusion: We determined that uPAR and CAIX levels were higher in the fluorouracil, epirubicin, and cyclophosphamide (FEC) chemotherapy group than in the control group, but there was no difference between the FEC and epirubicin/adriamycin chemotherapy groups in terms of basal and postchemotherapy uPAR, CAIX levels. Furthermore, uPAR is more specific, and CAIX is more sensitive in the diagnosis of breast cancer.