Ogunc Meral

Capsaicin inhibits cell proliferation by cytochrome c release in gastric cancer cells.

Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenesis is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-flourouracil (5-FU)-treated gastric cancer cells. In this study, the gastric cancer cell line HGC-27 was used and capsaicin used as a chemosensitizer and 5-flourouracil (5-FU) was used as chemotherapeutic. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay; supernatant levels of LDH and glucose were detected as biochemical markers of cell viability; cytochrome c and AIF were evaluated with western blot; and additionally, wound-healing assays were employed. Results suggested that capsaicin had significant anticancer abilities; such capsaicin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used for treating gastric carcinoma with 5-FU in vitro.

The syntheses, crystal structure, thermal analysis, and anticancer activities of novel dipicolinate complexes

[Cu(pydc)(eim)3]∙H2O (1), [Cu(pydc)(4hp)(H2O)] (2), and [Ni(pydc)(3hp)(H2O)2][Cu(pydc)(3hp)(H2O)2]∙3H2O (3) (H2pydc = 2,6-pyridinedicarboxylic acid or dipicolinic acid, eim = 2-ethylimidazole, 4hp = 4-hydroxypyridine, 3hp = 3-hydroxypyridine) were synthesized and characterized by elemental analysis, spectroscopic measurements (UV–vis and IR spectra), and single-crystal X-ray diffraction. Crystal analysis revealed that the complexes extended to 3-D supramolecular networks through intermolecular H-bonding and molecular interactions between the ligand moieties and water molecules. The thermal stabilities of complexes are investigated by thermogravimetry, differential thermogravimetry, and differential thermal analysis techniques. The effects of complexes on the proliferation of HT-1080 fibrosarcoma cells were investigated using the quick cell proliferation assay. The cell viability changes were found to depend on the concentrations and type of complex.

Syntheses of crystal structures and in vitro cytotoxic activities of new copper(II) complexes of pyridine-2,6-dicarboxylate

[Cu(pydc)(im)]n (1), [Cu(pydc)(mim)3]∙2H2O (2), [Cu(pydc)(ampy)(H2O)]∙H2O (3), and [Cu(pydc)(phen)][Cu(Hpydc)2] (4) (H2pydc = 2,6-pyridinedicarboxylic acid or dipicolinic acid, im = imidazole, mim = 2-methylimidazole, ampy = 2-amino-4-methylpyridine, and phen = 1,10-phenanthroline) were synthesized and characterized by elemental analysis, spectroscopic measurements (UV–vis and IR spectra) and single crystal X-ray diffraction. Complexes 1, 2 and 3 were studied by thermogravimetric analysis from ambient temperature to 1100 K under nitrogen and thermal stabilities were investigated. The effects of complexes on proliferation of fibrosarcoma cells were investigated using the Quick Cell Proliferation Assay. The cell viability changes depend on the concentrations and type of complexes. According to cell proliferation/viability data, 4 was determined to be the most cytotoxic.

Comparative proteomic analysis of fibrosarcoma and skin fibroblast cell lines

Comparative proteomic analysis of normal and cancer cell lines provides for a better understanding of the molecular mechanism of cancer development and is essential for developing more effective strategies for new biomarker or drug target discovery. The purpose of this study is to compare protein expression levels between fibrosarcoma and fibroblast cell lines. In our study, two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) and liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) techniques were carried out to compare the protein profile between fibrosarcoma and fibroblast cell lines. We prepared cell lysate samples to analyze intracellular proteins and secretome samples to analyze extracellular proteins in both cell lines. Our results revealed 13 upregulated proteins and 1 downregulated protein of which all of them identified in fibrosarcoma cell line after the comparison with fibroblast cell line cell lysates. When comparing secretome profiles of both cell lines, we found and identified 13 proteins only expressed in fibrosarcoma cell line. These identified proteins have common functions such as cell proliferation, cell differentiation, invasion, metastasis, and apoptosis in cancer. The data obtained from this study indicates that these proteins have importance on understanding the molecular mechanism of fibrosarcoma. These proteins may serve as candidate biomarkers and drug targets for future clinical studies.

GSM-like radiofrequency exposure induces apoptosis via caspase-dependent pathway in infant rabbits.

BACKGROUND There have been several Radio Frequency (RF) field researches on various populations and groups of different ages in recent years. However, the most important group for research has been declared as the pregnant women and their babies. OBJECTIVE The aim of the study was to analyse the effect on apoptotic factors of RF fields on newborn rabbit liver tissues. MATERIALS AND METHODS Cytochrome c and AIF (Apoptosis Inducing Factor) levels were measured by western blot and caspase 1, 3 and 9 activities were measured by colorimetric method. RESULTS Cytochrome c and AIF levels were not altered, but all caspase activities were increased in female infant rabbits that exposed to 1800 MHz GSM-like RF signals when they reached 1 month of age and caspase 1 and caspase 3 levels were decreased in male infant rabbits that exposed to 1800 MHz GSM-like RF signals between 15th and 22nd days of the gestational period. Results showed that 1800 MHz GSM-like RF exposure might lead to apoptosis in infant rabbits liver tissues. CONCLUSION According to the results, we suggest that postnatal RF exposure causes caspase dependent apoptosis in female infant rabbits liver tissues (Tab. 1, Fig. 2, Ref. 27).

Abstract 2808: Oxidative status of mouse azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer model and the effects of COX-2 inhibitor

Background: Colorectal cancer (CRC) is becoming increasingly common in Asian and European countries and still remains the second leading cause of cancer deaths in the United States. The prevention of carcinogenesis by anti-inflammatory agents including nonsteroidal anti-inflammatory drugs (NSAIDs), selective cyclooxygenase-2 (COX-2) inhibitors, and natural products is an area of considerable interest and research. Numerous anti-inflammatory agents have been identified as potential CRC chemopreventive agents but vary in their mechanism of action.The objective of this study is to explore the oxidative status of the mouse model of azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer, and effects of COX-2 inhibitor in these animals. Materials and Methods: Totally 40 mice were randomized divided to four groups All animals except control and Cox-2 inhibitor alone group received AOM/DSS to establish colitis-associated cancer model as reported elsewhere. Control group animals were fed with conventional mice diet. COX-2 preferential inhibitor meloxicam was used to minimize side effects such as gastrointestinal hemorrhage Meloxicam were used i.p. 5mg/kg tree times in a week for meloxicam alone and AOM/DSS + meloxicam group. Oxidative stress markers Superoxide dismutase (SOD), Glutation peroxidase (GPx), Malondialdehyde (MDA) and Advanced Oxidation Protein Products (AOPP) were measured by spectrophotometrically in sera. Results: The combination treatment of Meloxicam and AOM/DSS significantly increased (p Conclusion: Meloxicam and /or AOM/DSS treatment not caused lipid peroxidation, but increased the antioxidant enzymes and Advanced Oxidation Protein Products levels. Citation Format: Gorkem Kismali, Aykut Gokturk Uner, Ogunc Meral, Merve Alpay, Dilek Ulker Cakir, Funda Kosova, Tevhide Sel. Oxidative status of mouse azoxymethane (AOM)/dextran sulfate sodium (DSS)-induced colitis-associated cancer model and the effects of COX-2 inhibitor. [abstract]. In: Proceedings of the 107th Annual Meeting of the American Association for Cancer Research; 2016 Apr 16-20; New Orleans, LA. Philadelphia (PA): AACR; Cancer Res 2016;76(14 Suppl):Abstract nr 2808.

Abstract 3217: Capsaicin inhibits proliferation and chemosensitizes gastric carcinoma cells to 5-Fluorouracil

Proceedings: AACR Annual Meeting 2014; April 5-9, 2014; San Diego, CA Background: Capsaicin (trans-8-methyl-N-vanillyl-6-nonenamide) is the principal pungent component in hot peppers. The role of capsaicin in carcinogenic processes is quite controversial. Although some investigators suspect that capsaicin is a carcinogen, co-carcinogen, or tumor promoter, others have reported that it has chemopreventive and chemotherapeutic effects. Interestingly, capsaicin has been found to preferentially repress the growth of some transformed human and mouse cells. Although the antiproliferative activity of capsaicin has been ascribed to its ability to induce apoptosis. For example, The American Association for Cancer Research reports studies suggesting capsaicin is able to kill prostate cancer and lung cancer cells by causing them to undergo apoptosis. The present study aimed to evaluate the cytotoxicity and chemosensitizing activities of capsaicin alone and on 5-Flourouracil (5-FU) treated gastric carcinoma cells. Material and methods: In this study, the gastric cancer cell line HGC-27 was used. Cytotoxicity and chemosensitizing activities were analyzed with MTT assay. Capsaicin used a chemosensitizer and 5-FU was used as chemotherapeutic agent. Supernatant levels of Lactate dehydrogenases (LDH), Glucose (GLU) were detected as biochemical markers of cell viability. Additionally, cytochrome c and apoptosis inducing factor (AIF) were evaluated with western blot. Colonigenic assay and wound healing assays were also employed. Results: Capsaicin and 5-FU both detected cytotoxic and anticolonigenic on HGC-27 cells dose dependent manner after 24h/48h incubation. Both compounds were found more effective at 48h incubation. Furthermore, it is observed that the concentration of capsaicin higher than 12 µM may cause sensitization to 5-FU. Results suggested that capsaicin had significant anticancer and chemosensitizing abilities; such capsaicin were capable of causing multi-fold decreases in the half maximal inhibitory concentration IC50 value of 5-FU. The chemosensitizing ability of the capsaicin on HGC-27 metastatic lymph node from a gastric cancer patient diagnosed histological as undifferentiated carcinoma cells, in the present study is notable. The cytotoxic effect of capsaicin was observed cytochrome c activation dependent pathway. Conclusions: The continuing controversy surrounding consumption or topical application of capsaicin clearly suggests that more well-controlled epidemiologic studies are needed to evaluate the safety and efficacy of capsaicin use. In summary, the present study demonstrated that capsaicin has the potential to be used in chemosensitization for treating gastric carcinoma in vitro. Citation Format: Gorkem Kismali, Merve Alpay, Ogunc Meral, Funda Kosova, Dilek Ulker Cakir, Tevhide Sel. Capsaicin inhibits proliferation and chemosensitizes gastric carcinoma cells to 5-Fluorouracil. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 3217. doi:10.1158/1538-7445.AM2014-3217