Induction of apoptosis in human hormone-refractory prostate cancer cell lines by using resveratrol in combination with AT-101.

The aim of this study was to determine the appropriate doses of AT-101 and resveratrol combination in the in vitro hormone-refractory prostate cancer (PC) cell lines, in order to evaluate the cytotoxic and genotoxic effects of this combination on the proliferation of cancer cells, namely PC-3, DU-145 and LNCAP. Cytotoxicity in PC cell lines was analysed by using the XTT Cell Proliferation Assay. DNA damage was performed with the cell death assay. Apoptotic protein levels were performed by Roche Human Apoptosis Array. IC50 values were determined by XTT analysis. The strongest combined doses (100 µM resveratrol + 5µM AT-101) were found to have the strongest synergistic apoptotic and cytotoxic effects on DU-145 cells at 72 hr. While the combined use of resveratrol and AT-101 increased the expression of markers in apoptotic cell pathways on cells, a decrease in the expression of anti-apoptotic markers was detected (p Ë‚ 0.05). Combined applications of these compounds showed an important synergism in the hormone-refractory PC cell lines, and it was determined that after the post-translational modification, they were significantly effective on the apoptotic pathway. These results have revealed that the combination of resveratrol and AT-101 holds great expectation as a new chemotherapeutic application in the treatment of human prostate cancer.

Morin attenuates arsenic-induced toxicity in 3T3 embryonic fibroblast cells by suppressing oxidative stress, inflammation, and apoptosis: In vitro and silico evaluations.

This study aims to investigate the curative effects of Morin, a flavonoid, against arsenic toxicity in 3T3 embryonic fibroblast cells and its effect on the molecular mechanisms of cells. The cytotoxicity and viability of the cells were measured by MTT and LDH tests. Arsenic (0.74 µM) was used to trigger toxicity and Morin (50 µM) was used for treatment. The levels of oxidative stress biomarkers and the activities of antioxidant enzymes were measured by spectrophotometric method, and inflammatory markers were measured by ELISA method. While mRNA expression levels of Bax, Bcl-2 levels, and Caspase-3 activity were measured by qRT-PCR technique, TUNEL staining was performed to detect DNA breaks and DAPI staining to visualize nuclear changes. Protein structures were retrieved from the protein data bank. OpenBabel and Autodock programs were used for the molecular docking study. Morin rescued the 3T3 embryonic fibroblast cells exposed to arsenic. However, Arsenic decreased the activities of antioxidant enzymes in cells and significantly increased oxidative stress, inflammation, and apoptosis. Morin treatment reduced oxidative damage and TNF-α and IL-1ß levels. Arsenic-induced Caspase-3 mRNA expression level and Bax protein mRNA expression level were significantly increased, while Bcl-2 mRNA expression level was significantly decreased. While Caspase-3 mRNA expression level and Bax protein mRNA expression level decreased with morin treatment, Bcl-2 mRNA expression level increased significantly. Molecular docking study results showed good binding affinity of morin in SOD, GSH-Px, Bax, Bcl-2, Caspase-3, TNF-α, and IL-1ß structures. Morin showed antioxidant, anti-inflammatory, and anti-apoptotic effects against Arsenic-induced cellular toxicity.

Analysis of bioactive compounds using LC-ESI-MS/MS, cytotoxic, antimicrobial effects, and enzyme activities from Cyclotrichium origanifolium.

Cyclotrichium origanifolium is a medicinal plant belonging to the Lamiaceae family. In this study, phenolic content analysis, antimicrobial effects, and cytotoxic effects of extracts of C. origanifolium were investigated. In the extracts, phenolic compound analysis by the liquid chromatography-electrospray ionization-tandem mass spectrometry method, antimicrobial effect by the minimum inhibition concentration method, and cytotoxic effect on human dermal fibroblasts (HDF), glioblastoma cell (U87), ovarian adenocarcinoma cell (Skov-3), and human colorectal adenocarcinoma cell (CaCo-2) cancer cell lines were investigated. Cytotoxicity analyses were performed by the MTT method. In addition, the GST and AChE enzyme activities of the extracts were also measured. Around 18 compounds were detected in both the methanol and ethanol extract. It was found that the best antimicrobial effect on Gram-negative Pseudomonas aeruginosa was on methanol extract, while the ethanol extract was on Candida albicans fungus (respectively, 2.50 mg/ml, 5.0 µg/ml). A 500 µg/ml of methanol extract has been shown to have cytotoxic activity high effect on HDF cells. GST and AChE activity were found to decrease in a concentration-dependent manner.

In-vitro Antioxidant, Cytotoxic, Cholinesterase Inhibitory Activities and Anti-Genotoxic Effects of Hypericum retusum Aucher Flowers, Fruits and Seeds Methanol Extracts in Human Mononuclear Leukocytes.

The present study investigates the antioxidant, anticancer, anticholinesterase, anti-genotoxic activities and phenolic contents of flower, fruit and seed methanol extracts of Hypericum retusum AUCHER. The amounts of protocatechuic acid, catechin, caffeic acid and syringic acid in methanol extracts were determined by HPLC. Total phenolic content of H. retusum seed extract was found more than fruit and flower extracts. The DPPH free radical scavenging activity of flower and seed methanol extracts showed close activity versus BHT as control. Among three extracts of H. retusum only flower methanol extract was exhibited considerable cytotoxic activities against to HeLa and NRK-52E cell lines. Moreover, seed methanol extract showed both acetyl and butyrl-cholinesterase inhibitory activity. The highest anti-genotoxic effects were seen 25 and 50 µg/mL concentrations. In this study, the extracts showed a strong antioxidant and anti-genotoxic effect. The seed extract was more efficient- than extracts of fruit and flowers. Our results suggest that the antioxidant and anti-genotoxic effects of extracts depend on their phenolic contents. Further studies should evaluate the in-vitro and in-vivo the benefits of H. retusum seed methanol extracts.

Increased DNA damage and oxidative stress among silver jewelry workers.

Silver has long been valued as a precious metal, and it is used to make ornaments, jewelry, high-value tableware, utensils, and currency coins. Human exposures to silver and silver compounds can occur oral, dermal, or by inhalation. In this study, we investigated genotoxic and oxidative effects of silver exposure among silver jewelry workers. DNA damage in peripheral mononuclear leukocytes was measured by using the comet assay. Serum total antioxidative status (TAS), total oxidative status (TOS), total thiol contents, and ceruloplasmin levels were measured by using colorimetric methods among silver jewelry workers. Moreover, oxidative stress index (OSI) was calculated. Results were compared with non-exposed healthy subjects. The mean values of mononuclear leukocyte DNA damage were significantly higher than control subjects (p < 0.001). Serum TOS, OSI, and ceruloplasmin levels were also found to be higher in silver particles exposed group than those of non-exposed group (p < 0.001, p < 0.001, p < 0.01, respectively). However, serum TAS levels and total thiol contents of silver exposed group were found significantly lower (p < 0.05, p < 0.001, respectively). Exposure to silver particles among silver jewelry workers caused oxidative stress and accumulation of severe DNA damage.