Long-term impact of hypothyroidism during gestation and lactation on the mammary gland.

The functional differentiation of the mammary gland (MG) is fundamental for the prevention of mammary pathologies. This process occurs throughout pregnancy and lactation, making these stages key events for the study of pathologies associated with development and differentiation. Many studies have investigated the link between mammary pathologies and thyroid diseases, but most have ignored the role of thyroid hormone (TH) in the functional differentiation of the MG. In this work, we show the long-term impact of hypothyroidism in an animal model whose lactogenic differentiation occurred at low TH levels. We evaluated the ability of the MG to respond to hormonal control and regulate cell cycle progression. We found that a deficit in TH throughout pregnancy and lactation induces a long-term decrease in Rb phosphorylation, increases p53, p21, Cyclin D1 and Ki67 expression, reduces progesterone receptor expression, and induces nonmalignant lesions in mammary tissue. This paper shows the importance of TH level control during mammary differentiation and its long-term impact on mammary function.

Evaluation of cytotoxic and antitumoral properties of Tessaria absinthioides (Hook & Arn) DC, "pájaro bobo", aqueous extract.

Higher plants have provided various natural derived drugs used currently in western medicine. Tessaria absinthioides (Hook. & Arn.) DC, Asteraceae, is a native plant from South-America with reported ethnopharmacological and culinary uses. Despite recent scientific reports about plants properties, there is not a well conducted research about its anticancer and potential toxic effects. The current work demonstrates the plant aqueous extract composition; the in vitro induced cytotoxicity, and explores, in vivo, its oral toxicity and antitumoral effects. Composition of aqueous extract was determined by phytochemical reactions. Cytotoxicity was tested in tumoral (Hela, Gli-37, HCT-116 and MCF-7) and non-tumoral (HBL-100) cells, using MTT assay. Oral toxicity and the antitumor activity against colorectal carcinoma were studied in rodents. The chemical analysis revealed the presence of flavonoids, carbohydrates, sterols, terpenes and tannins. Cytotoxicity towards tumoral cells was observed (CV50: 3.0 to 14.8 υg/ml); while in non-tumoral cells, extracts evidenced a selective reduced toxicity (CV50: 29.5 υg/ml). Oral administration of the extract does not induce acute nor dose-repeated toxicity at doses up to 2000 mg/kg and 1000 mg/kg/day, respectively. The antitumoral effect was confirmed by a significant increase in a median survival from 24 weeks (non-treated) to 30 weeks (T. absinthioides treated). The present data indicate that T. absinthioides extract exhibits cytotoxicity against cancer cell lines, with no-toxic effects and significant antitumoral effects in colorectal cancer when is orally administrated. In conclusion, T. absinthioides possesses selective cytotoxicity and antitumoral activities, making its plant derivatives products promising for cancer research and treatment.

Evaluation of cytotoxic and antitumoral properties of Tessaria absinthioides (Hook & Arn) DC, "pájaro bobo", aqueous extract

Higher plants have provided various natural derived drugs used currently in western medicine. Tessaria absinthioides (Hook. & Arn.) DC, Asteraceae, is a native plant from South-America with reported ethnopharmacological and culinary uses. Despite recent scientific reports about plants properties, there is not a well conducted research about its anticancer and potential toxic effects. The current work demonstrates the plant aqueous extract composition; the in vitro induced cytotoxicity, and explores, in vivo, its oral toxicity and antitumoral effects. Composition of aqueous extract was determined by phytochemical reactions. Cytotoxicity was tested in tumoral (Hela, Gli-37, HCT-116 and MCF-7) and non-tumoral (HBL-100) cells, using MTT assay. Oral toxicity and the antitumor activity against colorectal carcinoma were studied in rodents. The chemical analysis revealed the presence of flavonoids, carbohydrates, sterols, terpenes and tannins. Cytotoxicity towards tumoral cells was observed (CV50: 3.0 to 14.8 μg/ml); while in non-tumoral cells, extracts evidenced a selective reduced toxicity (CV50: 29.5 μg/ml). Oral administration of the extract does not induce acute nor dose-repeated toxicity at doses up to 2000 mg/kg and 1000 mg/kg/day, respectively. The antitumoral effect was confirmed by a significant increase in a median survival from 24 weeks (non-treated) to 30 weeks (T. absinthioides treated). The present data indicate that T. absinthioides extract exhibits cytotoxicity against cancer cell lines, with no-toxic effects and significant antitumoral effects in colorectal cancer when is orally administrated. In conclusion, T. absinthioides possesses selective cytotoxicity and antitumoral activities, making its plant derivatives products promising for cancer research and treatment.

Las plantas superiores han provisto numerosos derivados naturales usados actualmente por la medicina occidental. Tessaria absinthioides (Hook & Arn) DC, Asteraceae, es una planta autóctona de Sudamérica con informes de uso etnofarmacológico y culinario. A pesar de los reportes científicos sobre las propiedades de esta planta, no existen estudios que caractericen sus efectos antitumorales ni sus efectos tóxicos. En el presente trabajo se describe la composición del extracto acuoso de T. absinthioides, sus propiedades citotóxicas in vitro, y explora in vivo la toxicidad oral y su capacidad de afectar la progresión de tumores. La composición se determinó mediante reacciones fitoquímicas. La citotoxicidad se estudió en líneas celulares tumorales (Gli-37, HeLa, HCT-116 y MCF-7) y no tumorales (HBL-100), utilizando el ensayo de MTT. La toxicidad oral de los extractos y su capacidad antitumoral sobre carcinoma colorrectal se analizaron en roedores. El análisis del extracto acuoso evidenció flavonoides, carbohidratos, esteroles, terpenos y taninos. La citotoxicidad sobre células tumorales resultó similar a la observada para el 5-fluoracilo (CV50: 3.0 a 14.8 μg/ml); mientras que, en células no tumorales, el efecto estuvo selectivamente reducido (CV50: 29.5 μg/ml). La administración oral del extracto no indujo toxicidad aguda ni a dosis repetidas (dosis hasta 2000 mg/kg y 1000 mg/kg/día, respectivamente). Los efectos antitumorales se confirmaron mediante un significativo aumento de la supervivencia en el grupo tratado con T. absinthioides. En conclusión, de acuerdo a los resultados obtenidos, T. absinthioides y sus derivados naturales representan un campo prometedor de estudio para la investigación en el tratamiento del cáncer.

Activation of human leukemic mast cell line LAD2 is modulated by dehydroleucodine and xanthatin.

The aim of the present study was to determine whether dehydroleucodine, xanthatin and 3-benzyloxymethyl-5H-furan-2-one inhibit the activation of human leukemic LAD2 mast cells induced by compound 48/80 or the calcium ionophore A23187. LAD2 cells were preincubated in the presence of test drugs and then challenged with the secretagogues. This study provides the first evidence in favor of the view that dehydroleucodine and xanthatin inhibit the degranulation of LAD2 cells, thus acting as human mast cell stabilizers. These molecules could be effective in the treatment of human diseases associated with inappropriate mast cell activation.