We synthesized eight new bipyridine and bipyrimidine gold (III) dithiocarbamate-containing complexes (C1–C8) and tested them in a panel of human cancer cell lines. We used osteosarcoma (MG-63), lung (A549), prostate (PC3 and DU145), breast (MCF-7), ovarian (A2780 and A2780cis, cisplatin- and doxorubicin-resistant), and cervical (ME-180 and R-ME-180, cisplatin resistant) cancer cell lines. We found that C2, C3, C6, and C7 were more cytotoxic than cisplatin in all cell lines tested and overcame cisplatin and doxorubicin resistance in A2780cis and R-ME-180 cells. In the PC3 prostate cancer cell line, the gold (III) complex C6 ([Au₂(BPM)(DMDTC)₂]Cl₄) induced apoptosis and double-stranded DNA breaks, modified cell cycle phases, increased Reactive Oxigen Species (ROS) generation, and reduced thioredoxin reductase and proteasome activities. It inhibited PC3 cell migration and was more cytotoxic against PC3 cells than normal human adipose-derived stromal cells. In mice bearing PC3 tumor xenografts, C6 reduced tumor growth by more than 70% without causing weight loss. Altogether, our results demonstrate the anticancer activity of these new gold (III) complexes and support the potential of C6 as a new agent for prostate cancer treatment.

Abscission is a highly coordinated developmental process by which plants control vegetative and reproductive organs load. Aiming at get new insights on flower abscission regulation, changes in the global transcriptome, metabolome and physiology were analyzed in ‘Thompson Seedless’ grapevine (Vitis vinifera L.) inflorescences, using gibberellic acid (GAc) spraying and shading as abscission stimuli, applied at bloom. Natural flower drop rates increased from 63.1 % in non-treated vines to 83 % and 99 % in response to GAc and shade treatments, respectively. Both treatments had a broad effect on inflorescences metabolism. Specific impacts from shade included photosynthesis inhibition, associated nutritional stress, carbon/nitrogen imbalance and cell division repression, whereas GAc spraying induced energetic metabolism simultaneously with induction of nucleotide biosynthesis and carbon metabolism, therefore, disclosing alternative mechanisms to regulate abscission. Regarding secondary metabolism, changes in flavonoid metabolism were the most represented metabolic pathways in the samples collected following GAc treatment while phenylpropanoid and stilbenoid related pathways were predominantly affected in the inflorescences by the shade treatment. However, both GAc and shade treated inflorescences revealed also shared pathways, that involved the regulation of putrescine catabolism, the repression of gibberellin biosynthesis, the induction of auxin biosynthesis and the activation of ethylene signaling pathways and antioxidant mechanisms, although often the quantitative changes occurred on specific transcripts and metabolites of the pathways. Globally, the results suggest that chemical and environmental cues induced contrasting effects on inflorescence metabolism, triggering flower abscission by different mechanisms and pinpointing the participation of novel abscission regulators. Grapevine showed to be considered a valid model to study molecular pathways of flower abscission competence acquisition, noticeably responding to independent stimuli.

The present investigation aimed to provide novel information on the chemical composition and in vitro bioaccessibility of bioactive compounds from raw citrus pomaces (mandarin varieties Clemenule and Ortanique and orange varieties Navel and Valencia). The effects of the baking process on their bioaccessibility was also assessed. Samples of pomaces and biscuits containing them as an ingredient were digested, mimicking the human enzymatic oral gastrointestinal digestion process, and the composition of the digests were analyzed. UHPLC-MS/MS results of the citrus pomaces flavonoid composition showed nobiletin, hesperidin/neohesperidin, tangeretin, heptamethoxyflavone, tetramethylscutellarein, and naringin/narirutin. The analysis of the digests indicated the bioaccessibility of compounds possessing antioxidant [6.6–11.0 mg GAE/g digest, 65.5–97.1 µmol Trolox Equivalents (TE)/g digest, and 135.5–214.8 µmol TE/g digest for total phenol content (TPC), ABTS, and ORAC-FL methods, respectively; significant reduction (p < 0.05) in Reactive Oxygen Species (ROS) formation under tert-butyl hydroperoxide (1 mM)-induced conditions in IEC-6 and CCD-18Co cells when pre-treated with concentrations 5–25 µg/mL of the digests], anti-inflammatory [significant reduction (p < 0.05) in nitric oxide (NO) production in lipopolysaccharide (LPS)-induced RAW264.7 macrophages], and antidiabetic (IC₅₀ 3.97–11.42 mg/mL and 58.04–105.68 mg/mL for α-glucosidase and α-amylase inhibition capacities) properties in the citrus pomaces under study. In addition, orange pomace biscuits with the nutrition claims “no-added sugars” and “source of fiber”, as well as those with good sensory quality (6.9–6.7, scale 1–9) and potential health promoting properties, were obtained. In conclusion, the results supported the feasibility of citrus pomace as a natural sustainable source of health-promoting compounds such as flavonoids. Unfractionated orange pomace may be employed as a functional food ingredient for reducing the risk of pathophysiological processes linked to oxidative stress, inflammation, and carbohydrate metabolism, such as diabetes, among others.

In the present work the feasibility of Tannat grape skin (TGS) as a functional ingredient in the formulation of two snacks (yogurt and biscuits) was studied. The research provided novel information on the effects of the food matrix and digestion process, under simulated human oral gastrointestinal conditions, in the bioaccessibility of TGS bioactive compounds composing of the snacks with health promoting properties (antioxidant, anti-inflammatory, and antidiabetic). TGS polyphenolic profile was analyzed by ultra-high performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS) finding mainly flavonoids, phenolic acids, and anthocyanins, which may exert antioxidant, anti-inflammatory, and carbohydrase inhibition capacities. TGS digest showed antioxidant and antidiabetic potential compared to the undigested sample (p < 0.05). Yogurt and biscuits with TGS were developed with the nutrition claims “no-added sugars” and “source of fiber” and were digested in vitro to evaluate the bioaccessibility of compounds with health promoting properties after food processing and digestion. After in vitro simulation of digestion, bioactive properties were enhanced for control and TGS snacks which may be attributed to the formation/release of compounds with health-promoting properties. Biscuits showed significant increase in ABTS antioxidant capacity and yogurt showed increased α-glucosidase inhibition capacity by the addition of TGS (p < 0.05). Polyphenols from TGS and bioactive peptides from snacks which may be released during digestion might be responsible for the observed bioactivities. Consumer’s acceptance of TGS yogurt and biscuits showed scores of 6.3 and 5.1 (scale 1–9), respectively, showing TGS yogurt had higher overall acceptance. Sensory profile assessed by check-all-that-apply + just-about-right (CATA+JAR) showed most of the attributes were evaluated as “just about right”, supporting good food quality. The developed yogurt presented adequate shelf-life parameters for 28 days. TGS yogurt with higher acceptability showed reduced ROS formation (p < 0.05) induced by tert-butyl hydroperoxide (1 mM) in CCD-18Co colon cells and RAW264.7 macrophages when pre-treated with concentrations 500–1000 and 100–500 µg/mL of the digests, respectively. Moreover, TGS yogurt digest pre-treatment reduced nitric oxide (NO) production (p < 0.05) in lipopolysaccharide (LPS)-induced RAW264.7 macrophages, showing anti-inflammatory potential. Bioactive peptides generated during lactic fermentation and digestion process may be contributors to intracellular effects. In conclusion, yogurt and biscuits with Tannat grape skin addition were obtained with nutrition claims “no-added sugars” and “source of fiber” with the potential to modulate key biochemical events associated with diabetes pathogenesis.