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

Measuring cell-type specific differential methylation in human brain tissue

The behavior of epigenetic mechanisms in the brain is obscured by tissue heterogeneity and disease-related histological changes. Not accounting for these confounders leads to biased results. We develop a statistical methodology that estimates and adjusts for celltype composition by decomposing neuronal and non-neuronal differential signal. This method provides a conceptual framework for deconvolving heterogeneous epigenetic data from postmortem brain studies. We apply it to find cell-specific differentially methylated regions between prefrontal cortex and hippocampus. We demonstrate the utility of the method on both Infinium 450k and CHARM data

Consequences of Intraspecific Variation in Seed Dispersal for Plant Demography, Communities, Evolution and Global Change

As the single opportunity for plants to move, seed dispersal has an important impact on plant fitness, species distributions and patterns of biodiversity. However, models that predict dynamics such as risk of extinction, range shifts and biodiversity loss tend to rely on the mean value of parameters and rarely incorporate realistic dispersal mechanisms. By focusing on the mean population value, variation among individuals or variability caused by complex spatial and temporal dynamics is ignored. This calls for increased efforts to understand individual variation in dispersal and integrate it more explicitly into population and community models involving dispersal. However, the sources, magnitude and outcomes of intraspecific variation in dispersal are poorly characterized, limiting our understanding of the role of dispersal in mediating the dynamics of communities and their response to global change. In this manuscript, we synthesize recent research that examines the sources of individual variation in dispersal and emphasize its implications for plant fitness, populations and communities. We argue that this intraspecific variation in seed dispersal does not simply add noise to systems, but, in fact, alters dispersal processes and patterns with consequences for demography, communities, evolution and response to anthropogenic changes. We conclude with recommendations for moving this field of research forward

Consequences of Intraspecific Variation in Seed Dispersal for Plant Demography, Communities, Evolution and Global Change

As the single opportunity for plants to move, seed dispersal has an important impact on plant fitness, species distributions and patterns of biodiversity. However, models that predict dynamics such as risk of extinction, range shifts and biodiversity loss tend to rely on the mean value of parameters and rarely incorporate realistic dispersal mechanisms. By focusing on the mean population value, variation among individuals or variability caused by complex spatial and temporal dynamics is ignored. This calls for increased efforts to understand individual variation in dispersal and integrate it more explicitly into population and community models involving dispersal. However, the sources, magnitude and outcomes of intraspecific variation in dispersal are poorly characterized, limiting our understanding of the role of dispersal in mediating the dynamics of communities and their response to global change. In this manuscript, we synthesize recent research that examines the sources of individual variation in dispersal and emphasize its implications for plant fitness, populations and communities. We argue that this intraspecific variation in seed dispersal does not simply add noise to systems, but, in fact, alters dispersal processes and patterns with consequences for demography, communities, evolution and response to anthropogenic changes. We conclude with recommendations for moving this field of research forward