Anticancer Activities of Meroterpenoids Isolated from the Brown Alga Cystoseira usneoides against the Human Colon Cancer Cells HT-29

Colorectal cancer (CRC) is one of the most common types of cancers and a leading cause of cancer death worldwide. The current treatment for CRC mainly involves surgery, radiotherapy, and chemotherapy. However, due to the side effects and the emergence of drug resistance, the search for new anticancer agents, pharmacologically safe and effective, is needed. In the present study, we have investigated the anticancer effects of eight algal meroterpenoids (AMTs, 1-8) isolated from the brown seaweed Cystoseira usneoides and their underlying mechanisms of action using HT-29, a highly metastatic human colon cancer cell line. All the tested meroterpenoids inhibited the growth of HT-29 malignant cells and were less toxic towards non-cancer colon cells, with the AMTs 1 and 5 exhibiting selectivity indexes of 5.26 and 5.23, respectively. Treatment of HT-29 cells with the AMTs 1, 2, 3, 4, 5, and 7 induced cell cycle arrest in G2/M phase and, in some instances, apoptosis (compounds 2, 3, and 5). Compounds 1-8 also exhibited significant inhibitory effects on the migration and/or invasion of colon cancer cells. Mechanistic analysis demonstrated that the AMTs 1, 2, 5, 6, 7, and 8 reduced phosphorylation levels of extracellular signal-regulated kinase (ERK) and the AMTs 2, 3, 4, 5, 7, and 8 decreased phosphorylation of c-JUN N-terminal kinase (JNK). Moreover, the AMTs 1, 2, 3, 4, 7, and 8 inhibited phosphorylation levels of protein kinase B (AKT) in colon carcinoma cells. These results provide new insights into the mechanisms and functions of the meroterpenoids of C. usneoides, which exhibit an anticancer effect on HT-29 colon cancer cells by inducing cell cycle arrest and apoptosis via the downregulation of ERK/JNK/AKT signaling pathways

Meroterpenoids from the Brown Alga Cystoseira usneoides as Potential Anti-Inflammatory and Lung Anticancer Agents

The anti-inflammatory and anticancer properties of eight meroterpenoids isolated from the brown seaweed Cystoseira usneoides have been evaluated. The algal meroterpenoids (AMTs) 1-8 were tested for their inhibitory effects on the production of the pro-inflammatory cytokines tumor necrosis factor (TNF-alpha), interleukin-6 (IL-6), and interleukin-1 beta (IL-1 beta), and the expression of cyclooxygenase-2 (COX-2), and inducible nitric oxide synthase (iNOS) in LPS-stimulated THP-1 human macrophages. The anticancer effects were assessed by cytotoxicity assays against human lung adenocarcinoma A549 cells and normal lung fibroblastic MRC-5 cells, together with flow cytometry analysis of the effects of these AMTs on different phases of the cell cycle. The AMTs 1-8 significantly reduced the production of TNF-alpha, IL-6, and IL-1 beta, and suppressed the COX-2 and iNOS expression, in LPS-stimulated cells (p < 0.05). The AMTs 1-8 displayed higher cytotoxic activities against A549 cancer cells than against MRC-5 normal lung cells. Cell cycle analyses indicated that most of the AMTs caused the arrest of A549 cells at the G2/M and S phases. The AMTs 2 and 5 stand out by combining significant anti-inflammatory and anticancer activities, while 3 and 4 showed interesting selective anticancer effects. These findings suggest that the AMTs produced by C. usneoides may have therapeutic potential in inflammatory diseases and lung cancer

Diterpenoids from the Brown Alga Rugulopteryx okamurae and Their Anti-Inflammatory Activity

Brown algae of the Family Dictyotaceae produce an array of structurally diverse terpenoids, whose biomedical potential in the anti-inflammatory area has been scarcely explored. Herein, the chemical study of the alga Rugulopteryx okamurae has led to the isolation of ten new diterpenoids: rugukadiol A (1), rugukamurals A–C (2–4), and ruguloptones A–F (6–10). The structures of the new compounds were established by spectroscopic means. Compound 1 exhibits an unprecedented diterpenoid skeleton featuring a bridged tricyclic undecane system. Compounds 2–10 belong to the secospatane class of diterpenoids and differ by the oxygenated functions that they contain. In antiinflammatory assays, the new diterpenoid 1 and the secospatanes 5 and 10 significantly inhibited the production of the inflammatory mediator NO in LPS-stimulated microglial cells Bv.2 and macrophage cells RAW264.7. Moreover, compounds 1 and 5 were found to strongly inhibit the expression of Nos2 and the pro-inflammatory cytokine Il1b in both immune cell lines

Emericellopsis maritima and Purpureocillium lilacinum Marine Fungi as a Source of Functional Fractions with Antioxidant and Antitumor Potential in Colorectal Cancer: A Preliminary Study

The marine environment is a promising source of natural products with possible pharmacological applications. In this sense, marine microorganisms, especially marine fungi, can produce bioactive compounds with various therapeutic properties. Colorectal cancer (CRC) represents a major health problem worldwide, since the treatments used to date are not capable of improving patient survival; that is why natural compounds from marine fungi offer a promising alternative. This study focused on evaluating the antitumor and antioxidant activity of fractions derived from the marine fungi E. maritima and P. lilacinum in two CRC cell lines T84 and SW480. Fractions Fr-EM6, Fr-EM7, Fr-EM8 and Fr-PLMOH-3 demonstrated potent cytotoxic activity in tested CRC cell lines with no activity in the non-tumor line. In particular, the Fr-PLMOH-3 fraction from P. lilacinum showed significant antiproliferative effects on T84 and SW480 cell lines and exhibited a greater cytotoxic effect on cancer stem cells compared to tumor cells. Furthermore, the Fr-EM8 fraction from E. maritima demonstrated a strong antioxidant capacity. These findings highlight the potential of compounds of marine origin as effective and selective antitumor agents for the treatment of CRC. Further studies are needed to explore the underlying mechanisms and potential clinical applications of these bioactive fractions and compounds

Uso de oxilipinas y sus derivados como agentes antiinflamatorios

La invención se refiere al uso de ácidos grasos monohidroxilados, en particular de oxilipinas derivadas de ácidos α-linolénico y linoleico, así como al uso de fracciones, extractos o biomasa de microalgas que contienen dichos ácidos, para su empleo como antiinflamatorios y quimiopreventivos en la enfermedad inflamatoria intestinal.Españ

Estudio de supervivencia de pacientes menores de 18 años de edad con diagnóstico de cáncer atendidos en el Hospital Universitario San Ignacio-Centro Javeriano de Oncología entre octubre de 2010 y marzo de 2016

ResumenIntroducción: El cáncer infantil ocasiona importante mortalidad. El objetivo es caracterizar y determinar la sobrevida de un centro especializado. Métodos: Análisis de supervivencia en menores de 18 años de edad, diagnosticados con cáncer del 01/10/2010 al 31/03/2016. Se analizaron variables sociodemográficas (edad, sexo, seguridad social y zona de residencia) y clínicas (tipo de cáncer y categorización del riesgo). Se utilizó el método de Kaplan-Meier y Log-Rank Test. Resultados: 135 pacientes, con una edad promedio 7,4 años (DE 4,84), la mayoría de sexo masculino y pertenecientes al régimen contributivo. Las neoplasias más frecuentes fueron leucemias y tumores de sistema nervioso central, predominancia de alto riesgo. La supervivencia global fue del 75 % y la supervivencia libre de evento fue del 60 %. Los tumores sólidos y de alto riesgo presentaron mayor mortalidad. Conclusiones: La supervivencia global a 5 años es similar a los datos internacionales. La mayoría de los tumores sólidos eran de alto riesgo, probablemente asociados a mayor tiempo de evolución

Estudio de supervivencia de pacientes menores de 18 años de edad con diagnóstico de cáncer atendidos en el Hospital Universitario San Ignacio-Centro Javeriano de Oncología entre octubre de 2010 y marzo de 2016

ResumenIntroducción: El cáncer infantil ocasiona importante mortalidad. El objetivo es caracterizar y determinar la sobrevida de un centro especializado. Métodos: Análisis de supervivencia en menores de 18 años de edad, diagnosticados con cáncer del 01/10/2010 al 31/03/2016. Se analizaron variables sociodemográficas (edad, sexo, seguridad social y zona de residencia) y clínicas (tipo de cáncer y categorización del riesgo). Se utilizó el método de Kaplan-Meier y Log-Rank Test. Resultados: 135 pacientes, con una edad promedio 7,4 años (DE 4,84), la mayoría de sexo masculino y pertenecientes al régimen contributivo. Las neoplasias más frecuentes fueron leucemias y tumores de sistema nervioso central, predominancia de alto riesgo. La supervivencia global fue del 75 % y la supervivencia libre de evento fue del 60 %. Los tumores sólidos y de alto riesgo presentaron mayor mortalidad. Conclusiones: La supervivencia global a 5 años es similar a los datos internacionales. La mayoría de los tumores sólidos eran de alto riesgo, probablemente asociados a mayor tiempo de evolución

Phorbol Diesters and 12-Deoxy-16-hydroxyphorbol 13,16-Diesters Induce TGF alpha Release and Adult Mouse Neurogenesis

A small library of phorbol 12,13-diesters bearing low lipophilicity ester chains was prepared as potential neurogenic agents in the adult brain. They were also used in a targeted UHPLC-HRMS screening of the latex of Euphorbia resinifera. Two new 12-deoxy-16-hydroxyphorbol 13,16-diesters were isolated, and their structures were deduced using two-dimensional NMR spectroscopy and NOE experiments. The ability of natural and synthetic compounds to stimulate transforming growth factor alpha (TFG alpha) release, to increase neural progenitor cell proliferation, and to stimulate neurogenesis was evaluated. All compounds that facilitated TGF alpha release promoted neural progenitor cell proliferation. The presence of two acyloxy moieties on the tigliane skeleton led to higher levels of activity, which decreased when a free hydroxyl group was at C-12. Remarkably, the compound bearing isobutyryloxy groups was the most potent on the TGF alpha assay and at inducing neural progenitor cell proliferation in vitro, also leading to enhanced neurogenesis in vivo when administered intranasally to mice.This work was supported by the Spanish Ministerio de Ciencia, Innovacion y Universidades (grant nos RTI2018-099908-BC21 and RTI2018-099908-B-C22 MICINN/FEDER granted to CC and RHG, respectively) and Consejeria de Economia, Conocimiento, Empresas y Universidades Junta de Andalucia (grant no FEDER-ANDALUCIA sol2018-00106647-tra). We thank the "Servicio de experimentacion y produccion animal (SEPA) de la Universidad de Cadiz" as well as the "Servicios Centrales de apoyo a la investigacion en Ciencias de la Salud (SCICS) de la Universidad de Cadiz" and "Servicios centrales de Ciencia Cadiz"

The oldest record of Hemiauchenia Gervais and Ameghino (Mammalia, Cetartiodactyla) in South America: Comments about its paleobiogeographic and stratigraphic implications

The South American camelids belong to the Tribe Lamini; this Tribe originated in North America and arrived in South America during the “Great American Biotic Interchange”. The goals of this paper are: (i) to describe the specimen MAM-70, the oldest record of Hemiauchenia Gervais and Ameghino in South America; (ii) to analyze this specimen from a stratigraphic point of view; (iii) to update the distribution and stratigraphic ranges of Lamini in South America; and (iv) to discuss its dispersal pattern to South America. The finding of Hemiauchenia sp. in late Pliocene Chapadmalalan sediments cropping out at the city of Olavarría (Buenos Aires Province, Argentina) represents the oldest record of a Lamini taxon in South America. This finding refutes the hypotheses that consider the genus Lama as the first North American immigrant and those considering that Hemiauchenia and Palaeolama arrived in South America after the closure of the Central America land bridge, during the early–middle Pleistocene. In turn, this specimen corroborates the hypothesis of the dispersal of Lamini from North America to South America, which considered that Palaeolama dispersed after Hemiauchenia, in a later and isolated event. In addition, this finding suggests the possibility that a form closely related to the North American Hemiauchenia macrocephala could have dispersed to South America during the Pliocene, thus originating the South American forms of Hemiauchenia and Lama.Fil: Gasparini, Germán Mariano. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: de Los Reyes, Leonardo Martín. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; ArgentinaFil: Francia, Analia. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. División Paleontología Vertebrados; Argentina. Consejo Nacional de Investigaciones Científicas y Técnicas; ArgentinaFil: Scherer, Carolina Saldanha. Universidade Federal do Recôncavo da Bahia; BrasilFil: Poire, Daniel Gustavo. Consejo Nacional de Investigaciones Científicas y Técnicas. Centro Científico Tecnológico Conicet - La Plata. Centro de Investigaciones Geológicas. Universidad Nacional de La Plata. Facultad de Ciencias Naturales y Museo. Centro de Investigaciones Geológicas; Argentin