TRIM29 (ATDC) exhibits a contextual function in cancer, but appears to exert a tumor suppressor role in breast cancer. Here we show that TRIM29 is often silenced in primary breast tumors and cultured tumor cells as a result of aberrant gene hypermethylation. RNAi-mediated silencing of TRIM29 in breast tumor cells increased their motility, invasiveness, and proliferation in a manner associated with increased expression of mesenchymal markers (N-cadherin and vimentin), decreased expression of epithelial markers (E-cadherin and EpCAM), and increased expression and activity of the oncogenic transcription factor TWIST1, an important driver of the epithelial-mesenchymal transition (EMT). Functional investigations revealed an inverse relationship in the expression of TRIM29 and TWIST1, suggesting the existence of a negative regulatory feedback loop. In support of this relationship, we found that TWIST1 inhibited TRIM29 promoter activity through direct binding to a region containing a cluster of consensus E-box elements, arguing that TWIST1 transcriptionally represses TRIM29 expression. Analysis of a public breast cancer gene expression database indicated that reduced TRIM29 expression was associated with reduced relapse-free survival (RFS), increased tumor size, grade, and metastatic characteristics. Taken together, our results suggest that TRIM29 acts as a tumor suppressor in breast cancer through its ability to inhibit TWIST1 and suppress EMT.

Objective We aimed to investigate the serum concentrations of vitamin B12, folate and homocysteine in children diagnosed with attention deficit hyperactivity disorder (ADHD) or autism spectrum disorder (ASD) and healthy controls. Materials and methods Serum vitamin B12, folate and homocysteine concentrations were measured in 118 children (48 children diagnosed with ADHD, 35 children diagnosed with ASD and 35 healthy controls). Symptom severity in the ADHD and ASD groups was evaluated by the Childhood Autism Rating Scale and Turgay-DSM-IV-Based Screening and Assessment Scale for Disruptive Behavior Disorders. Multivariate analysis of covariance was used to evaluate the effects of diagnosis and gender on biochemical parameters. Results The ADHD and ASD groups and the healthy controls differed significantly regarding vitamin B12 and homocysteine concentrations, but not folate levels. Patients with ASD had the lowest vitamin B12 and the highest homocysteine levels. Vitamin B12 levels correlated negatively with hyperactivity and/orimpulsivity and oppositionality symptoms in children with ADHD. There were no relationships between psychometric evaluations and laboratory measurements in children with ASD. Gender did not affect vitamin concentrations. Conclusion Previous studies found that vitamin B12 was reduced while homocysteine was elevated among patients with ADHD and ASDs. Our results also support those reported previously. Oppositionality and hyperactivity and/orimpulsivity may be related to vitamin B12 and homocysteine levels in children with ADHD. Further studies are required to define the role of these parameters and effects on the etiology and clinical manifestations of ASD and ADHD.

Reactive oxygen species (ROS) are thought to be among the initiating insults that drive carcinogenesis; however, beyond the mutagenic properties of ROS, it is unclear how reactive oxygen species and response to redox imbalance may shape cancer phenotype. We have previously observed that basal activity of the powerfully oncogenic transcription factor NF-κB in cultured breast cancer and other tumor cell lines is dependent upon the DNA damage-responsive kinase ATM. Here we show that, in MDA-MB-231 and HeLa cells, basal ATM-dependent NF-κB activation occurs through a canonical DNA damage-responsive signaling pathway as knockdown of two proteins involved in this signaling pathway, ERC1 and TAB1, results in loss of NF-κB basal activity. We further show that knockdown of ATM in MDA-MB-231, a breast cancer line with a pronounced mesenchymal phenotype, results in the reversion of these cells to an epithelial morphology and gene expression pattern. Culture of MDA-MB-231 and HeLa cells on the antioxidant N-acetyl cysteine (NAC) blunted NF-κB transcriptional activity, and long-term culture on low doses of NAC resulted in coordinate reductions in steady-state ROS levels, acquisition of an epithelial morphology, as well as upregulation of epithelial and downregulation of mesenchymal marker gene expression. Moreover, these reversible effects are attributable, at least in part, to downregulation of ATM-dependent NF-κB signaling in MDA-MB-231 cells as RNAi-mediated knockdown of the NF-κB subunit RelA or its upstream activator TG2 produced similar alterations in phenotype. We conclude that chronic activation of ATM in response to persistent ROS insult triggers continual activation of the oncogenic NF-κB transcriptional complex that, in turn, promotes aggressive breast cancer phenotype.

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.

PL and ALA may have a potential value as a therapeutic agent for patients with acute promyelocytic leukemia.

In this study, the antimicrobial, antioxidant and antitumor activity of ethanol extracts obtained from Phlomis russeliana (Sims.) Lag. ex Benth. (Lamiaceae) were evaluated. Disc diffusion and microdilution methods were used to test the extracts for antimicrobial activity against seven bacteria strains (Bacillus cereus ATCC 7064, Bacillus subtilis ATCC 6633, Staphylococcus aureus ATCC 6538P, Escherichia coli ATCC 10538, Proteus vulgaris ATCC 6899, Salmonella typhimurium CCM 5445 and Pseudomonas aeruginosa ATCC 27853) and four yeast strains (Kluyveromyces fragilis ATCC 8608, Rhodotorula rubra ATCC 70403, Debaryomyces hansenii DSM 70238 and Candida albicans ATCC 10239). Notably, they were more effective against the yeast strains than the bacterial strains. Of the yeast cultures, D. hanseii was among the most susceptible, having an inhibition zone of 16.2 mm with minimum inhibitory concentrations (MICs) and minimum fungicidal concentrations (MFCs) of 64(128)µg/ml, respectively. For cytotoxic determination, Caco-2 cells were cultured as per ATCC protocol, and were treated with log concentrations (5-80 mg/ml) of P. russeliana. The potency of cell growth inhibition for each extract was expressed as an IC50 value. Moreover, oxidant capacity was evaluated via TOC assay. This product induced antiproliferative activity of 31.33% at 40 mg/ml and 20.96% at 80 mg/ml, without toxic effects on cells, although the oxidant capacity was decreased to 27.06 ± 0.7 nm in the 80 mg/mlapplied group compared to 47.9 ± 1.8 nm in the untreated one. Advanced pharmacological studies are needed to further evaluate P. russeliana for distinctive features.

Background: Rutin is a strong antioxidant molecule and it has advantageous over other flavonoids due to it is a nontoxic and nonoxidizable molecule. The concept of dual therapy of anti-cancer drugs with natural compounds has become a very promising approach in new strategy to treatment. The aim of this study was to evaluate the antiproliferative and apoptotic effects of rutin flavonoids and its efficacy in enhancing the anticancer effects of 5-FU (5-fluorouracil) and oxaliplatin against colon cancer cells. Material and Methods: Caco-2 human colon cancer cells were treated with rutin and/or anticancer drugs (5-FU and oxaliplatin), cell viability and apoptotic parameters were examined. Cell viability was determined by MTT assay. Apoptotic markers (cleaved caspase 3, cleaved PARP and phosphor-Bad) were determined using specific enzyme-linked immunosorbent assay kits. Caspase-8 and caspase-9 were analyzed by colorimetric activity assay kit. DNA fragmentation was analyzed by agarose gel electrophoresis. Results: The exposure Caco-2 human colon cancer cells to rutin, 5-FU and oxaliplatin resulted growth inhibition in a dose- and time-dependent manner. Cell viability assay shows that rutin inhibiting growth of Caco-2 cells at high concentrations (over 1000 μM). Combination with rutin markedly enhanced 5-FU and oxaliplatin growth inhibiting effects on Caco-2 cells. Results suggested that rutin had significant anticancer abilities; such rutin were capable of causing multifold decreases in the half maximal inhibitory concentration IC50 value of 5-FU and oxaliplatin. This flavonoid increased the levels of proteins associated with apoptotic cell death (phospho-Bad, cleaved caspase 3 and cleaved PARP) alone and combination. The activities of caspase 8 and caspase 9 were stimulated by the combination treatment of rutin and oxaliplatin then alone. DNA fragmentation was observed only on combination treatment. Conclusions: Combined treatment with rutin and anticancer drugs (5-FU and/or oxaliplatin) is more effective than the individual treatments of drugs at inhibiting growth of Caco-2 cells. The use of lower 5-FU and oxaliplatin doses, with similar effects, could be also useful to reduce possible adverse effects of these drugs. However, further studies at molecular level are required to elucidate chemopreventive and chemotherapeutic effects of rutin on colon cancer. Citation Format: Farnoud Nasiri, Gorkem Kismali, Merve Alpay, Funda Kosova, Dilek Ulker Cakir, Tevhide Sel. Rutin enhances the antiproliferative effect of 5-FU and oxaliplatin in colon cancer cells. [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 2177.

Journal of Cellular Neuroscience and Oxidative Stress is an online journal that publishes original research articles, reviews and short reviews on the molecular basis of biophysical, physiological and pharmacological processes that regulate cellular function, and the control or alteration of these processes by the action of receptors, neurotransmitters, second messengers, cation, anions, drugs or disease. Areas of particular interest are four topics. They are; A-Ion Channels (Na +-K + Channels, Clchannels, Ca 2+ channels, ADP-Ribose and metabolism of NAD + , Patch-Clamp applications) B-Oxidative Stress (Antioxidant vitamins, antioxidant enzymes, metabolism of nitric oxide, oxidative stress, biophysics, biochemistry and physiology of free oxygen radicals) C-Interaction Between Oxidative Stress and Ion Channels in Neuroscience (Effects of the oxidative stress on the activation of the voltage sensitive cation channels, effect of ADP-Ribose and NAD + on activation of the cation channels which are sensitive to voltage, effect of the oxidative stress on activation of the TRP channels in neurodegenerative diseases such Parkinson's and Alzheimer's diseases) D-Gene and Oxidative Stress (Gene abnormalities. Interaction between gene and free radicals. Gene anomalies and iron. Role of radiation and cancer on gene polymorphism)