Narcin Palavan-Unsal

Increased Expression of EZH2, a Polycomb Group Protein, in Bladder Carcinoma

Introduction: Recent experiments have demonstrated that polycomb group gene enhancer zeste homolog 2 (EZH2) is highly expressed in many cancer types. Therefore, we aim to demonstrate EZH2 gene expression in transitional cell bladder cancer. Patients and Methods: The reverse transcriptase-polymerase chain reaction (RT-PCR) was used for detection of EZH2 mRNA levels in healthy and cancerous human bladder specimens. Also, expression of the particular protein was determined by Western blotting and immunohistochemistry to confirm RT-PCR results. Results: Gradually increased expression of EZH2 was detected by mRNA and protein levels in highly advanced bladder cancer specimens. In contrast, 100% of control subjects were negative for EZH2 expression. The expression of EZH2 was more frequent in G3 (92%) than G1-G2 (62–63%) and more frequent in T1-2 (72–85%) than Ta (56%). Western blot analysis results confirm the RT-PCR results. Conclusions: EZH2 overexpression precedes high frequencies of proliferation and the gradual advance of bladder cancer. These observations suggest that deregulated expression of EZH2 is associated with bladder carcinoma.

Serum Adipocytokine Levels in Prostate Cancer Patients

Introduction: We estimated the circulating levels of adipocytokines such as adiponectin and leptin in nonobese nondiabetic prostate cancer (PCa) patients and compared the results with controls and benign prostate hyperplasia (BPH) patients. Material and Methods: Fifty patients with PCa, 20 patients with BPH and 50 healthy volunteers were entered into the study. Their blood samples were investigated for adipocytokines with the ELISA method. Results: Adiponectin levels were determined as 8.9 and 5.5 μg/ml for the same patients. Leptin concentration was 14.78 ng/ml in organ-confined PCa patients, and 15.24 ng/ml in advanced PCa patients. In control patients, adiponectin and leptin levels were 18.4 and 12.98 ng/ml, respectively. Conclusion: Serum adipocytokine levels of PCa patients were significantly different from those of controls and BPH patients who were not obese or diabetic. Therefore, further molecular investigation of these adipocytokines will help understand the mechanism.

Bag-1L is a Stress-withstand Molecule Prevents the Downregulation of Mcl-1 and c-Raf Under Control of Heat Shock Proteins in Cisplatin Treated HeLa Cervix Cancer Cells

BACKGROUND Cisplatin, a DNA damaging agent, induces apoptosis through increasing DNA fragmentation. However, identification of intrinsic resistance molecules against Cisplatin is vital to estimate the success of therapy. Bag-1 (Bcl-2-associated anthanogene) is one anti-apoptotic protein involved in drug resistance impacting on therapeutic efficiency. Elevated levels of this protein are related with increase cell proliferation rates, motility and also cancer development. For this reason, we aimed to understand the role of Bag-1 expression in Cisplatin- induced apoptosis in HeLa cervix cancer cells. Cisplatin decreased cell viability in time- and dose-dependent manner in wt and Bag-1L+HeLa cells. Although, 10 μM Cisplatin treatment induced cell death within 24h by activating caspases in wt cells, Bag-1L stable transfection protected cells against Cisplatin treatment. To assess the potential protective role of Bag-1, we first checked the expression profile of interacting anti-apoptotic partners of Bag-1. We found that forced Bag-1L expression prevented Cisplatin-induced apoptosis through acting on Mcl-1 expression, which was reduced after Cisplatin treatment in wt HeLa cells. This mechanism was also supported by the regulation of heat shock protein (Hsp) family members, Hsp90 and Hsp40, which were involved in the regulation Bag-1 interactome including several anti-apoptotic Bcl-2 family members and c-Raf.

The effect of putrescine and difluoromethylornithine on cell division activity of wheat in different ploidy level

Abstract Effects of exogenous putrescine (Put) and difluoromethylornithine (DFMO) on seed germination, root growth, mitotic activity and mitotic chromosome behavior were investigated in Triticum monococcum (2x), Triticum durum (4x) and Triticum aestivum (6x). Put and DFMO affected all three species, but diploid species was the most affected one in respect to seed germination, mitotic index and the occurrence of abnormality than the others. Reduction of the root growth in Put and DFMO treated samples was due to the reduction of mitotic activity in three species used in this research.

Calreticulin is a fine tuning molecule in epibrassinolide‐induced apoptosis through activating endoplasmic reticulum stress in colon cancer cells

Epibrassinolide (EBR), a member of brassinostreoids plant hormones with cell proliferation promoting role in plants, is a natural polyhydroxysteroid with structural similarity to steroid hormones of vertebrates. EBR has antiproliferative and apoptosis‐inducing effect in various cancer cells. Although EBR has been shown to affect survival and mitochondria‐mediated apoptosis pathways in a p53‐independent manner, the exact molecular targets of EBR are still under investigation. Our recent SILAC (Stable Isotope Labeling by Amino Acids in Cell Culture) data showed that the most significantly altered protein after EBR treatment was calreticulin (CALR). CALR, a chaperone localized in endoplasmic reticulum (ER) lumen, plays role in protein folding and buffering Ca2+ ions. The alteration of CALR may cause ER stress and unfolded protein response correspondingly the induction of apoptosis. Unfolded proteins are conducted to 26S proteasomal degradation following ubiquitination. Our study revealed that EBR treatment caused ER stress and UPR by altering CALR expression causing caspase‐dependent apoptosis in HCT 116, HT29, DLD‐1, and SW480 colon cancer cells. Furthermore, 48 h EBR treatment did not caused UPR in Fetal Human Colon cells (FHC) and Mouse Embryonic Fibroblast cells (MEF). In addition our findings showed that HCT 116 colon cancer cells lacking Bax and Puma expression still undergo UPR and related apoptosis. CALR silencing and rapamycin co‐treatment prevented EBR‐induced UPR and apoptosis, whereas 26S proteasome inhibition further increased the effect of EBR in colon cancer cells. All these findings showed that EBR is an ER stress and apoptotic inducer in colon cancer cells without affecting non‐malignant cells.

Breast Cancer and Flavonoids as Treatment Strategy

Breast cancer is the most prevalent cancer type among women. Despite recent progress in early detection and therapeutic strategies, the rate of mortality is increasing. Antiestrogens or aromatase inhibitors are preferred to treat the women diagnosed with estrogen-receptor (ER) positive tumors. However, breast tumors usually show intra-tumoral heterogeneity with ER-positive and -negative cells. The advanced breast cancer cells lose the estrogen responsiveness and become aggressive by developing new strategies for rapid proliferation such as mutations in cell cycle machinery. New promising drugs are still being investigating against these types of tumors especially to overcome acquired resistance against chemotherapeutic drugs; however, a successful treatment for metastatic tumors is still unclear. Flavonoids, with various pharmacological activities, are plant or fungus secondary metabolites present in human diet. In plants, beside their role in pigmentation, they may also act as messengers, regulators and cell cycle inhibitors. Therefore, they are being tested in ovarian, cervical as well as breast cancer. Due to the positive correlation between flavonoids-rich diet and lower risk of cancer, flavonoids are referred as chemopreventive agents. The current chapter emphasizes the therapeutic potential of flavonoids and their synthetic analogues as anti-cancer agents in breast cancer providing new insights into the molecular mechanisms.