Mitochondrial and sarcoplasmic reticulum abnormalities in cancer cachexia: altered energetic efficiency?

BACKGROUND: Cachexia is a wasting condition that manifests in several types of cancer, and the main characteristic is the profound loss of muscle mass. METHODS: The Yoshida AH-130 tumor model has been used and the samples have been analyzed using transmission electronic microscopy, real-time PCR and Western blot techniques. RESULTS: Using in vivo cancer cachectic model in rats, here we show that skeletal muscle loss is accompanied by fiber morphologic alterations such as mitochondrial disruption, dilatation of sarcoplasmic reticulum and apoptotic nuclei. Analyzing the expression of some factors related to proteolytic and thermogenic processes, we observed in tumor-bearing animals an increased expression of genes involved in proteolysis such as ubiquitin ligases Muscle Ring Finger 1 (MuRF-1) and Muscle Atrophy F-box protein (MAFBx). Moreover, an overexpression of both sarco/endoplasmic Ca(2+)-ATPase (SERCA1) and adenine nucleotide translocator (ANT1), both factors related to cellular energetic efficiency, was observed. Tumor burden also leads to a marked decreased in muscle ATP content. CONCLUSIONS: In addition to muscle proteolysis, other ATP-related pathways may have a key role in muscle wasting, both directly by increasing energetic inefficiency, and indirectly, by affecting the sarcoplasmic reticulum-mitochondrial assembly that is essential for muscle function and homeostasis. GENERAL SIGNIFICANCE: The present study reports profound morphological changes in cancer cachectic muscle, which are visualized mainly in alterations in sarcoplasmic reticulum and mitochondria. These alterations are linked to pathways that can account for energy inefficiency associated with cancer cachexia.

A new analytical concept based on chemistry and toxicology for herbal extracts analysis: From phenolic composition to bioactivity.

Studies regarding the bioactivity of teas are mainly based on the phenolic composition and in vitro antioxidant activity of the herbal species used in their preparation. The aim of this study was to compare the in vitro and ex vivo antioxidant activity, cytotoxic/antiproliferative activity against cancer cells, the inhibitory activity of α-amylase, α-glucosidase and angiotensin I-converting enzymes, as well as the inhibition of DNA-induced fission of the peroxyl radical, in relation to aqueous extracts of Camellia sinensis var. sinensis (CS), Ilex paraguariensis (IP), Aspalathus linearis (AL) and an optimised extract (OT) containing the three herb species. A bivariate and multivariate statistical approach was employed to associate functional activities with individual phenolic composition. The CS and OT extracts showed the highest levels of hesperidin, quercetin-3-rutinoside, (-)-epigallocatechin-3-gallate and isoquercitrin. The CS and OT extracts showed the highest antioxidant activity, greater ability to inhibit α-amylase and proliferation of HCT8 cells, and greater ability to reduce Folin-Ciocalteu reagent. The AL extract, which is the major source of quercetin-3-rutinoside, hesperidin and isoquercitrin, showed the highest ability to inhibit α-glucosidase, the inhibition of LDL oxidation and protection of human erythrocytes. The IP extract showed the highest inhibition of lipoperoxidation in brain homogenate of Wistar rats, antihypertensive activity, and A549 cell proliferation; chlorogenic acid was its major phenolic compound. In general, the in vitro functionality of each extract was dependent on its chemical composition and the OT extract presented the most varied phenolic composition, and biological activity similar to the CS sample. In conclusion, the mixture of CS, AL, and IP represents a chemical and functional-based strategy to develop functional teas.

Camu-camu seed (Myrciaria dubia) - From side stream to anantioxidant, antihyperglycemic, antiproliferative, antimicrobial, antihemolytic, anti-inflammatory, and antihypertensive ingredient.

Camu-camu (Myrciaria dubia) seeds are discarded without recovering the bioactive compounds. The main aim of the present work was to optimise the solvent mixture to extract higher total phenolic content and antioxidant capacity of camu-camu seeds. The optimised solvent system increased the extraction of phenolic compounds, in which vescalagin and castalagin were the main compounds. The optimised extract displayed antioxidant capacity measured by different chemical and biological assays, exerted antiproliferative and cytotoxic effects against A549 and HCT8 cancer cells, antimicrobial effects, protected human erythrocytes against hemolysis, inhibited α-amylase and α-glucosidase enzymes and presented in vitro antihypertensive effect. Additionally, the optimized extract inhibited human LDL copper-induced oxidation in vitro and reduced the TNF-α release and NF-κB activation in macrophages cell culture. Thus, the use of camu-camu seed showed to be a sustainable way to recover bioactive compounds with in vitro functional properties.

Antioxidant activity of phenolics compounds from sugar cane (Saccharum officinarum L.) juice.

Phenolic compounds in sugar cane (Saccharum officinarum L.) juice were identified and quantified by analytical high performance liquid chromatography and photodiode array detection, showing the predominance of flavones (apigenin, luteolin and tricin derivatives), among flavonoids, and of hydroxycinnamic, caffeic and sinapic acids, among phenolic acids, representing a total content of around 160 mg/L. A tricin derivative was present in the highest proportion (>10% of the total). The phenolic extract obtained from sugar cane juice showed a protective effect against in vivo MeHgCl intoxication and potent inhibition of ex vivo lipoperoxidation of rat brain homogenates, indicating a potential use for beneficial health effects and/or therapeutic applications.