Multiple studies have shown that psychological distress in epithelial ovarian cancer (EOC) patients is associated with worse quality of life and poor treatment adherence. This may influence chemotherapy response and prognosis. Moreover, although stress hormones can reduce cisplatin efficacy in EOC treatment, their effect on the integrity of DNA remains poorly understood. In this study, we investigated whether norepinephrine and epinephrine can induce DNA damage and modulate cisplatin-induced DNA damage in three EOC cell lines. Our data show that norepinephrine and epinephrine exposure led to increased nuclear γ-H2AX foci formation in EOC cells, a marker of double-strand DNA breaks. We further characterized norepinephrine-induced DNA damage by subjecting EOC cells to alkaline and neutral comet assays. Norepinephrine exposure caused DNA double-strand breaks, but not single-strand breaks. Interestingly, pre-treatment with propranolol abrogated norepinephrine-induced DNA damage indicating that its effects may be mediated by β-adrenergic receptors. Lastly, we determined the effects of norepinephrine on cisplatin-induced DNA damage. Our data suggest that norepinephrine reduced cisplatin-induced DNA damage in EOC cells and that this effect may be mediated independently of β-adrenergic receptors. Taken together, these results suggest that stress hormones can affect DNA integrity and modulate cisplatin resistance in EOC cells.

Background: Breast cancer (BC) is the most common cancer afflicting Puerto Rican women and accounts for more cancer-related deaths in this population than any other cancer. Methods: Demographic, anthropometric, family history, and lifestyle data, as well as DNA repair capacity (DRC), were compared in 465 BC cases and 661 controls. Crude and multiple...

Sandalwood essential oil (SEO) is extracted from Santalum trees. Although α‐santalol, a main constituent of SEO, has been studied as a chemopreventive agent, the genotoxic activity of the whole oil in human breast cell lines is still unknown. The main objective of this study was to assess the cytotoxic and genotoxic effects of SEO in breast adenocarcinoma (MCF‐7) and nontumorigenic breast epithelial (MCF‐10A) cells. Proteins associated with SEO genotoxicity were identified using a proteomics approach. Commercially available, high‐purity, GC/MS characterized SEO was used to perform the experiments. The main constituents reported in the oil were (Z)‐α‐santalol (25.34%), (Z)‐nuciferol (18.34%), (E)‐β‐santalol (10.97%), and (E)‐nuciferol (10.46%). Upon exposure to SEO (2–8 μg/mL) for 24 hours, cell proliferation was determined by the MTT assay. Alkaline and neutral comet assays were used to assess genotoxicity. SEO exposure induced single‐ and double‐strand breaks selectively in the DNA of MCF‐7 cells. Quantitative LC/MS‐based proteomics allowed identification of candidate proteins involved in this response: Ku70 (p = 1.37E − 2), Ku80 (p = 5.8E − 3), EPHX1 (p = 3.3E − 3), and 14‐3‐3ζ (p = 4.0E − 4). These results provide the first evidence that SEO is genotoxic and capable of inducing DNA single‐ and double‐strand breaks in MCF‐7 cells.

Although GABA neurotransmission has been suggested as a mechanism forValeriana officinaliseffects, CNS depression can also be evoked by inhibition of ionotropic (iGluR) and metabotropic glutamate receptors (mGluR). In this study, we examined if aqueous valerian extract interacted with glutamatergic receptors. Freshly prepared aqueous valerian extract was incubated with rat cortical synaptic membranes in presence of 20 nM [³H]Glutamate. Aqueous valerian extract increased [³H]Glutamate binding from 1 × 10⁻⁷to 1 × 10⁻³ mg/mL. In the presence of (2S,1^′S,2^′S)‐2‐(Carboxycyclopropyl)glycine (LCCG‐I) and (2S,2^′R,3^′R)‐2‐(2^′,3^′‐Dicarboxycyclopropyl)glycine (DCG‐IV), Group II mGluR agents, valerian extract markedly decreased [³H]Glutamate binding, while (2S)‐2‐amino‐3‐(3,5‐dioxo‐1,2,4‐oxadiazolidin‐2‐yl) propanoic acid) (quisqualic acid, QA), Group I mGluR agonist, increased [³H]Glutamate binding. At 0.05 mg/mL aqueous valerian extract specifically interacted with kainic acid NMDA and AMPA receptors. Valerenic acid, a marker compound forValeriana officinalis, increased the [³H]Glutamate binding after 1.6 × 10⁻² mg/mL, and at 0.008 mg/mL it interacted only with QA (Group I mGluR). The selective interactions of valerian extract and valerenic acid with Group I and Group II mGluR may represent an alternative explanation for the anxiolytic properties of this plant.

Estrogen-receptor-positive (ER+) tumors employ complex signaling that engages in crosstalk with multiple pathways through genomic and non-genomic regulation. A greater understanding of these pathways is important for developing improved biomarkers that can better determine treatment choices, risk of recurrence and cancer progression. Deficiencies in DNA repair capacity (DRC) is a hallmark of breast cancer (BC); therefore, in this work we tested whether ER signaling influences DRC. We analyzed the association between ER positivity (% receptor activation) and DRC in 270 BC patients, then further stratified our analysis by HER2 receptor status. Our results show that among HER2 negative, the likelihood of having low DRC values among ER- women is 1.92 (95% CI: 1.03, 3.57) times the likelihood of having low DRC values among ER+ women, even adjusting for different potential confounders (p<0.05); however, a contrary pattern was observed among HER2 positives women. In conclusion, there is an association between DRC levels and ER status, and this association is modified by HER2 receptor status. Adding a DNA repair capacity test to hormone receptor testing may provide new information on defective DNA repair phenotypes, which could better stratify BC patients who have ER+ tumors. ER+/HER2- tumors are heterogeneous, incompletely defined, and clinically challenging to treat; the addition of a DRC test could better characterize and classify these patients as well as help clinicians select optimal therapies, which could improve outcomes and reduce recurrences.

Cubiu is a vegetable of Solanaceae family, native to the Amazon, which is widely distributed through Brazil, Peru, and Colombia. It is used in food, medicine, and cosmetics by native populations. Research has shown that cubiu extracts have antioxidant activities with great biological relevance. We performed a phytochemical screening to identify the main chemical groups that could confer antioxidant activity to this extract. Several tests and qualitative precipitation specific staining for major classes of secondary metabolites were used. Antioxidant capacityin vitrotests (DPPH and ABTS) were also used to assess the extract’s ability to sequester free radicals of 70% hydroethanolic and aqueous extracts of cubiu flour. Alkaloids, organic acids, phenols, flavonoid glycosides, and coumarins were found in the hydroethanolic extract while the aqueous extract presented anthocyanins, gums, tannins and mucilage, amino groups, and volatile and fixed acids. Forin vitrotests, theIC50value obtained in the DPPH assay was 606.3 ± 3.5 μg/mL while that for the ABTS assay was 290.3 ± 10.7 µg/mL. Although cubiu extracts present chemical compounds directly related to antioxidant activity, our results show that it has a low antioxidant activity. Additional studies will be needed to isolate and characterize specific compounds to further assess antioxidant activity.