Selective cytotoxic effect of Annona muricata L. in HCC1954 (HER2+) breast cancer cells / Efecto citotóxico selectivo de Annona muricata L. en células HCC1954 (HER2+) de cáncer de mama

Annona muricata Linn. (Annonaceae) is a tropical plant with multiple beneficial health effects including anticancer properties. In breast cancer patients, overexpression of the HER2 oncoprotein corresponds to a poor prognosis, thus the main purpose of this study was to evaluate the cytotoxicity of ethanolic extracts from dried and fresh leaf of A. muricata on HER2+ breast cancer cells. MTT assays were performed and IC50 determined in HCC1954 (HER2+) cells, as well as in MCF7 (HER-) and peripheral blood mononuclear cells (PBMC) used as controls. Total polyphenol content evaluation and phytochemical screening were also performed. The cytotoxic effect of A. muricata extracts (125-1000 µg/mL) was dose-dependent and cell-type specific. The extracts exhibited higher cytotoxicity against HCC1954 than MCF7 cells, but weak toxicity against PBMC. This is the first report of the cytotoxic effect of A. muricata on HCC1954 cells, highlighting its potential for treating anti-estrogen-resistant breast cancers and low toxicity against PBMC.

Annona muricata Linn. (Annonaceae) es una planta tropical con múltiples efectos benéficos en la salud incluyendo propiedades antitumorales. En pacientes con cáncer de mama la sobreexpresión del oncogen HER2 corresponde a un mal pronóstico, por lo que el objetivo principal de este estudio fue evaluar la citotoxicidad de extractos etanólicos de hojas secas y frescas de A. muricata en células tumorales de mama HER2+. Se aplicaron pruebas de MTT y se determinaron IC50en células HCC1954 (HER2+); se utilizaron células MCF7 (HER-) y células mononucleares de sangre periférica (PBMC) como control. Se valoró también el contenido en polifenoles totales, y se realizó un tamizaje fitoquímico. El efecto citotóxico de los extractos de A. muricata (125-1000 µg/mL) fue dosis-dependiente y específico para cada tipo celular. Los extractos presentaron mayor actividad citotóxica contra HCC1954 en comparación con MCF7 y baja toxicidad contra PBMC. Este es el primer reporte del efecto citotóxico de A. muricata en HCC1954 y destaca su potencial terapéutico para tratamiento de cáncer de mama resistentes a antiestrógeno y baja citotoxicidad contra PBMC.

Effects of Zinc on the Right Cardiovascular Circuit in Long-Term Hypobaric Hypoxia in Wistar Rats.

Hypobaric hypoxia under chromic conditions triggers hypoxic pulmonary vasoconstriction (HPV) and right ventricular hypertrophy (RVH). The role of zinc (Zn) under hypoxia is controversial and remains unclear. We evaluated the effect of Zn supplementation in prolonged hypobaric hypoxia on HIF2α/MTF-1/MT/ZIP12/PKCε pathway in the lung and RVH. Wistar rats were exposed to hypobaric hypoxia for 30 days and randomly allocated into three groups: chronic hypoxia (CH); intermittent hypoxia (2 days hypoxia/2 days normoxia; CIH); and normoxia (sea level control; NX). Each group was subdivided (n = 8) to receive either 1% Zn sulfate solution (z) or saline (s) intraperitoneally. Body weight, hemoglobin, and RVH were measured. Zn levels were evaluated in plasma and lung tissue. Additionally, the lipid peroxidation levels, HIF2α/MTF-1/MT/ZIP12/PKCε protein expression and pulmonary artery remodeling were measured in the lung. The CIH and CH groups showed decreased plasma Zn and body weight and increased hemoglobin, RVH, and vascular remodeling; the CH group also showed increased lipid peroxidation. Zn administration under hypobaric hypoxia upregulated the HIF2α/MTF-1/MT/ZIP12/PKCε pathway and increased RVH in the intermittent zinc group. Under intermittent hypobaric hypoxia, Zn dysregulation could participate in RVH development through alterations in the pulmonary HIF2α/MTF1/MT/ZIP12/PKCε pathway.

Chronic stress decreases ornithine decarboxylase expression and protects against 1,2-dimethylhydrazine-induced colon carcinogenesis.

Biological response to stress depends on the type, timing, and severity of the stressor. Acute stressful environments may positively activate molecular and cellular mechanisms to favor adaptation; however, chronic stress is often associated with detrimental health effects. Colon cancer (CC) is one of the leading causes of death associated with cancer and has been mentioned as a stress-related disease. In the present work, the effect of chronic stress on the initial phase of CC was evaluated, and special emphasis was placed on ornithine decarboxylase (ODC) expression and polyamines for their role in hyperproliferative diseases. BALB/c mice (n = 5/group) were administered the pro-carcinogen 1,2-dimethylhydrazine (DMH) for 8 weeks (20 mg/kg body weight/week) to induce colon carcinogenesis, and then exposed for 4 weeks to two physical stressors: restraint and forced-swimming. Distal colon inflammatory lesions and histomorphological changes were evaluated by hematoxylin-eosin staining; plasma corticosterone levels, colon ODC expression, and urinary polyamines were determined by competitive ELISA, RT-qPCR, Western Blot, and HPLC, respectively. The short-term exposure to DMH triggered colon inflammation, initiated colon carcinogenesis and increased ODC expression; meanwhile, the exposure to chronic stress activated the hypothalamic-pituitary-adrenal (HPA) axis, elicited the production of plasmatic corticosterone, and decreased ODC expression. The exposure of DMH-treated mice to chronic stress counteracted the inflammatory effect of DMH and maintained ODC homeostasis. In early phase of carcinogenesis, the exposure of DMH-treated mice to chronic stress had a positive effect against colon inflammation and maintained ODC homeostasis. The cross-talk between corticosterone, ODC expression, and inflammation in a tumor environment is discussed.

Immunomodulatory Effect of Lactobacillus casei in a Murine Model of Colon Carcinogenesis.

We previously reported beneficial effects of the probiotic strain Lactobacillus casei 393 in hindering colon carcinogenesis in a 1,2-dimethylhydrazine (DMH)-induced BALB/c mouse model of colon cancer. In the present study, we investigated the effect of preventive administration of L. casei 393 on the levels of selected pro- and anti-inflammatory circulating cytokines, as well as subpopulations of splenic T cells. The resulting experimental data on IFNγ, TNFα, IL-10, and colon histological features demonstrated that administration of L. casei 2 weeks before DMH treatment impaired the pro-inflammatory effect of DMH, while maintaining the levels of the three cytokines as well as colon histology; it also modulated splenic CD4+, CD8+, and NK T cell subpopulations. The preventive administration of L. casei to DMH-treated mice increased IL-17A synthesis and Treg percentages, further indicating a tumor-protecting role. Together, the results suggest that the colon-cancer-protective properties of L. casei 393 involve the dampening of inflammation through cytokine homeostasis and the maintenance of a healthy T cell subpopulation dynamic. For these reasons, probiotics such as L. casei may contribute to the health of the host as they promote optimal control of the immune response. Further, they may be used as prophylactic agents in combination with standard therapies against colon cancer.

Species diversity, structure and dynamics of two populations of an endangered species, Magnolia dealbata (Magnoliaceae).

Little is known about the ecology and demography of the genus Magnolia. Magnolia dealbata Zucc. is an endangered species endemic to Mexico. Two contrasting populations of M. dealbata (one from the grasslands and other from a secondary cloud forest) were studied. We asked the following questions: (a) Are size structure (diameter at breast height, DBH) and infrutescence production significantly different between the two populations? (b) What are the populations' growth rates (lambda) based on an initial 1987 study? (c) Are the associated species diversity indices of these M. dealbata populations significantly different? The results show no significant differences between the population size structure (p=.094); the growth rates of the populations were 0.992 in grassland and 1.053 in secondary cloud forest. The number of infrutescences produced in year 2001 and DBH relationship were significantly linear (p<.001) in both populations, and there was no significant difference (p>.01) between their slopes. The diversity indices were not significantly different (p>.05), and only 54% of the species were common to both sites. Our study suggests that both populations are relatively stable and that the management history could impact more on the species composition than on the diversity indices.