Capsaicinoids and Their Effects on Cancer: The "Double-Edged Sword" Postulate from the Molecular Scale.

Capsaicinoids are a unique chemical species resulting from a particular biosynthesis pathway of hot chilies (Capsicum spp.) that gives rise to 22 analogous compounds, all of which are TRPV1 agonists and, therefore, responsible for the pungency of Capsicum fruits. In addition to their human consumption, numerous ethnopharmacological uses of chili have emerged throughout history. Today, more than 25 years of basic research accredit a multifaceted bioactivity mainly to capsaicin, highlighting its antitumor properties mediated by cytotoxicity and immunological adjuvancy against at least 74 varieties of cancer, while non-cancer cells tend to have greater tolerance. However, despite the progress regarding the understanding of its mechanisms of action, the benefit and safety of capsaicinoids' pharmacological use remain subjects of discussion, since CAP also promotes epithelial-mesenchymal transition, in an ambivalence that has been referred to as "the double-edge sword". Here, we update the comparative discussion of relevant reports about capsaicinoids' bioactivity in a plethora of experimental models of cancer in terms of selectivity, efficacy, and safety. Through an integration of the underlying mechanisms, as well as inherent aspects of cancer biology, we propose mechanistic models regarding the dichotomy of their effects. Finally, we discuss a selection of in vivo evidence concerning capsaicinoids' immunomodulatory properties against cancer.

Proangiogenic Effect of Affinin and an Ethanolic Extract from Heliopsis longipes Roots: Ex Vivo and In Vivo Evidence.

Angiogenesis, the formation of new blood vessels, underlies tissue development and repair. Some medicinal plant-derived compounds can modulate the angiogenic response. Heliopsis longipes, a Mexican medicinal plant, is widely used because of its effects on pain and inflammation. The main bioactive phytochemicals from H. longipes roots are alkamides, where affinin is the most abundant. Scientific studies show various medical effects of organic extracts of H. longipes roots and affinin that share some molecular pathways with the angiogenesis process, with the vasodilation mechanism of action being the most recent. This study investigates whether pure affinin and the ethanolic extract from Heliopsis longipes roots (HLEE) promote angiogenesis. Using the aortic ring rat assay (ex vivo method) and the direct in vivo angiogenesis assay, where angioreactors were implanted in CD1 female mice, showed that affinin and the HLEE increased vascular growth in a dose-dependent manner in both bioassays. This is the first study showing the proangiogenic effect of H. longipes. Further studies should focus on the mechanism of action and its possible therapeutic use in diseases characterized by insufficient angiogenesis.

The Short-Term Effects of Roux-en-Y Gastric Bypass on Renal Excretion of Sodium and Its Association with Blood Pressure.

INTRODUCTION: Bariatric surgery has been shown to be effective in reducing weight and has benefits, such as lowering blood pressure. An increase in urinary sodium excretion has been suggested as a possible mechanism. This study explored changes in sodium excretion and their correlation with blood pressure after Roux-en-Y gastric bypass. MATERIALS AND METHODS: This study was conducted on 28 obese participants with body mass index (BMI) of 44.54 ± 7.81 kg/m2 who underwent gastric bypass. Before surgery and at the third and sixth months after gastric bypass, blood pressure, urinary sodium concentration, 24-hour (24-h) urinary sodium excretion, and fractional excretion of sodium were evaluated. In addition, serum sodium and potassium levels were determined. Nonparametric tests were used to analyze the data. RESULTS: Blood pressure decreased after surgery and remained at low levels over the 3- and 6-month periods. The urinary sodium concentration increased at 3 months after surgery; however, the 24-h urinary sodium excretion and urine volume decreased. Interestingly, although some associations between variables were observed, significant correlations between the 24-h urinary sodium excretion and the systolic, diastolic, and mean blood pressures were found. In addition, the urine volume was higher in the sixth month than in the third month following surgery. CONCLUSIONS: In the months immediately following surgery, a low-salt and low-volume diet favors decreases in urine volume and 24-h urinary sodium excretion. In addition, in the sixth month after surgery, an association between blood pressure and 24-h urinary sodium excretion was observed.

Validation of a predictive index of neoplasia in unexplained weight loss / Validación de un índice predictivo de neoplasia en pérdida de peso inexplicada

Background: Involuntary weight loss (IWL) is associated with a bad prognosis. A causal diagnosis is difficult and the priority is to identify those patients at risk of a serious underlying disease, such as malignant neoplasia. Objective: External validation of a prognostic index of neoplasia in patients with IWL. Methods: Patients referred for IWL from 2005 to 2014 to the Department of Internal Medicine, of a specialty care hospital in Mexico City were studied. Al of them underwent an evaluation consisting of medical history, physical examination and basic laboratory studies, those patients without an apparent cause of IWL, were included. A probability of neoplasia according to Hernández prognostic index was calculated. Complementary diagnostic studies were performed until a causal diagnosis was reached, or the cases were classified as "unknown cause", if the etiology was not possible to find after one year of follow-up. A binarian logistic model was constructed with five variables age, leucocyte count, albumin, lactic dehydrogenase and alkaline phosphatase levels, and a prediction rule was developed. Results: 130 Patients were included and 45 of them (30%) had a neoplastic cause of IWL. The prediction rule according to Hernández criteria, correctly classified 65% of the patients (sensitivity 29%, Specificity 85%, positive predictive value 50% and negative predictive value 69%). When the original index was modified in two categories (high and low probability), it showed a sensitivity of 84.4% and a negative predictive value of 85.7%. Conclusion: The Hernández index has a limited value as a screening tool.

Introducción: la pérdida involuntaria de peso es un factor de mal pronóstico. Su diagnóstico causal es difícil y es prioritario identificar los casos que tienen una enfermedad grave subyacente. Objetivo: validar un índice pronóstico de neoplasia en pacientes con pérdida involuntaria de peso. Métodos: pacientes referidos por pérdida involuntaria de peso de 2005 a 2014, fueron evaluados mediante historia clínica y exámenes básicos de laboratorio; en el estudio fueron incluidos los pacientes sin causa aparente después de la evaluación. Se calculó la probabilidad de neoplasia, según el índice de Hernández. Se realizaron estudios complementarios hasta identificar una causa o fueron clasificados como "causa desconocida", si no se encontró la etiología después de un año de seguimiento. Se construyó un modelo de regresión logística binaria con las variables edad, cifras de leucocitos, albúmina, deshidrogenasa láctica y fosfatasa alcalina; con la ecuación resultante se predijo neoplasia como causa de pérdida involuntaria de peso. Resultados: se incluyeron 130 pacientes, 45 tuvieron causa neoplásica (30%). La ecuación de predicción clasificó correctamente a 65% de los sujetos analizados (especificidad 85%, sensibilidad 29%, valor predictivo positivo 50%, valor predictivo negativo 69%). Al modificarse el índice original en dos categorías (probabilidad alta y baja), mostró una sensibilidad del 84.4% y un valor predictivo negativo del 85.7%. Conclusión: el índice tuvo baja sensibilidad, lo que limita su uso como prueba de tamizaje.

Phaseolus acutifolius Lectin Fractions Exhibit Apoptotic Effects on Colon Cancer: Preclinical Studies Using Dimethilhydrazine or Azoxi-Methane as Cancer Induction Agents.

Phaseolus acutifolius (Tepary bean) lectins have been studied as cytotoxic molecules on colon cancer cells. The toxicological profile of a Tepary bean lectin fraction (TBLF) has shown low toxicity in experimental animals; exhibiting anti-nutritional effects such as a reduction in body weight gain and a decrease in food intake when using a dose of 50 mg/kg on alternate days for six weeks. Taking this information into account, the focus of this work was to evaluate the effect of the TBLF on colon cancer using 1,2-dimethylhydrazine (DMH) or azoxy-methane/dextran sodium sulfate (AOM/DSS) as colon cancer inductors. Rats were treated with DMH or AOM/DSS and then administered with TBFL (50 mg/kg) for six weeks. TBLF significantly decreased early tumorigenesis triggered by DMH by 70%, but without any evidence of an apoptotic effect. In an independent experiment, AOM/DSS was used to generate aberrant cryptic foci, which decreased by 50% after TBLF treatment. TBLF exhibited antiproliferative and proapoptotic effects related to a decrease of the signal transduction pathway protein Akt in its activated form and an increase of caspase 3 activity, but not to p53 activation. Further studies will deepen our knowledge of specific apoptosis pathways and cellular stress processes such as oxidative damage.