Betaine suppresses cell proliferation by increasing oxidative stress-mediated apoptosis and inflammation in DU-145 human prostate cancer cell line

Kacar, Sedat/0000-0002-0671-8529; kar, fatih/0000-0001-8356-9806; Sahinturk, Varol/0000-0003-2317-3644WOS: 000483691000002PubMed: 31368044Prostate cancer is the main cause of cancer-related mortality in men around the world and an important health problem. DU-145 human prostate cancer cells provide an opportunity to investigate prostate cancer. Betaine has a number of anticancer effects, such as inactivation of carcinogens, inhibition of cancer cell proliferation, angiogenesis, and metastasis. However, there is no study investigating the effects of betaine on DU-145 cells. The aim of this study was to evaluate the effects of different concentrations of betaine on the oxidative stress, apoptosis, and inflammation on DU-145 cells. Firstly, we proved the cytotoxic activity of betaine (0 to 150 mg/ml) on DU-145 cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the optimal concentration of betaine. Then, by employing the doses found in MTT, the levels of antioxidant (GSH, SOD, CAT, and TAS) and oxidant (MDA and TOS) molecules, pro-inflammatory cytokines (TNF-a and IL-6), apoptotic proteins (CYCS and CASP3), and DNA fragmentation were measured. Morphological changes and apoptosis were evaluated using H&E technique, Bax and Bcl-2 immunohistochemistry. Results suggested that betaine caused oxidative stress, inflammation, inhibition of cell growth, apoptosis, and morphological alterations in DU-145 cells dose-dependently. Furthermore, treatments with increasing betaine concentrations decreased the antioxidant levels in cells. We actually revealed that betaine, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. In conclusion, betaine may act as a biological response modifier in prostate cancer treatment in a dose-dependent manner

High Concentrations of Boric Acid Trigger Concentration-Dependent Oxidative Stress, Apoptotic Pathways and Morphological Alterations in DU-145 Human Prostate Cancer Cell Line

Kacar, Sedat/0000-0002-0671-8529; Sahinturk, Varol/0000-0003-2317-3644WOS: 000512037400012PubMed: 31066018Boric acid is known to regulate the proliferation of cancer cells. Prostate cancer is among the types of cancer with high mortality in men. There are a few numbers of studies investigating the effects of boric acid on prostate cancer cells. The objective of the present study was to assess the effects of boric acid at concentrations higher than that can be achieved in blood by dietary intake on DU-145 human prostate cancer cells for 24 h. Firstly, we determined the cytotoxic activity of boric acid (0 to 12.5 mM) on DU-145 human prostate cancer cells by using 3-(4, 5-dimethylthiazol, 2-yl)-2, 5-diphenyl tetrazolium bromide (MTT) and defined the IC50 concentration of boric acid. Then, by employing the doses found in MTT, the levels of antioxidant-oxidant molecules and apoptotic proteins were measured and morphological changes were evaluated. We have concluded that boric acid caused oxidative stress, inhibition of cell growth, apoptosis, and morphological alterations in a concentration-dependent manner in DU-145 cells. Furthermore, treatments with increasing boric acid concentrations decreased the antioxidant levels in cells. We actually revealed that boric acid, known as an antioxidant, may prevent cell proliferation by acting as an oxidant in certain doses. Although the high IC50 concentration of boric acid is perceived to be negative, we think it provides important background for subsequent studies

Bexarotene inhibits cell proliferation by inducing oxidative stress, DNA damage and apoptosis via PPAR gamma/ NF-kappa B signaling pathway in C6 glioma cells

Gliomas are one of the most aggressive brain tumors with a poor prognosis in the central nervous system. Bexarotene is a third-generation retinoid X receptor agonist that is promising in the treatment of both cancer and neurodegenerative diseases. In this study, we aimed to investigate the cytotoxic and anti-proliferative effects of bexarotene in C6 glioma cells through the PPAR gamma/NF-kappa B pathway. In the study, first cytotoxic bexarotene concentrations for C6 cells were detected, and then apoptosis profile, reactive oxygen species (ROS), total antioxidant (TAS), 8-hydroxy-2 '-deoxyguanosine (8-OHdG) and nuclear factor-kappa B (NF-kappa B) levels in the cells were determined. In addition, peroxisome proliferator-activated receptor gamma (PPAR gamma) mRNA expression analysis was carried out. As a result, we detected concentration- and time-dependent antiproliferative effects of bexarotene on C6 cells. We found that bexarotene treatment decreased NF-kappa B and TAS levels and increased PPAR gamma and 8-OHdG levels in C6 cells. Bexarotene enhanced PPAR gamma expression in a dose-dependent manner when compared to the control group (P < 0.01). Furthermore, we determined that bexarotene-induced apoptotic C6 cells enhanced through Annexin V-FITC/PI staining and caspase-3/-7 activation analyses since phosphatidylserine level on the outer surface of the cell membrane and caspase-3/-7 activities were increased in the cells treated with bexarotene. In conclusion, bexarotene treatment in C6 glioma cells could modulate apoptosis profile, DNA damage, ROS production, and reduction of TAS levels through inhibition of NF-kappa B by enhancing PPAR gamma expression

Effects of metformin on lipopolysaccharide induced inflammation by activating fibroblast growth factor 21

Lipopolysaccharide (LPS) is a component of the cell wall of Gram-negative bacteria that produces endotoxemia, which may cause septic shock. Metformin (MET) is a widely used hypoglycemic drug that exhibits anti-inflammatory properties. Fibroblast growth factor 21 (FGF21) is an endocrine polypeptide that affects glucose and lipid metabolism, and also possesses anti-inflammatory properties. We investigated the effects of MET and FGF21 on inflammation due to LPS induced endotoxemia in male rats. Animals were divided into five groups: control, LPS, pre-MET LPS, LPS + 1 h MET and LPS + 3 h MET. Serum levels of alanine aminotransferase, aspartate aminotransferase, FGF2, interleukin-10 and tumor necrosis factor alpha were measured. Malondialdehyde, myeloperoxidase and FGF21 levels were measured in liver tissue samples. Histopathology of all groups was assessed using hematoxylin and eosin stained sections. LPS caused severe inflammatory liver damage. MET exhibited a partially protective effect and reduced inflammation significantly. FGF21 is produced in the liver following inflammation and MET may increase its production