Metabolic and Oxidative Stress Management Heterogeneity in a Panel of Breast Cancer Cell Lines.

Metabolic alterations are recognized as one of the hallmarks of cancer. Among these, alterations in mitochondrial function have been associated with an enhanced production of Reactive Oxygen Species (ROS), which activate ROS-regulated cancer cell signaling pathways. Breast cancer is the main cancer-related cause of death for women globally. It is a heterogeneous disease with subtypes characterized by specific molecular features and patient outcomes. With the purpose of identifying differences in energy metabolism and the oxidative stress management system in non-tumorigenic, estrogen receptor positive (ER+) and triple negative (TN) breast cancer cells, we evaluated ROS production, protein enzyme levels and activities and profiled energy metabolism. We found differences in energetic metabolism and ROS management systems between non-tumorigenic and cancer cells and between ER+ and TN breast cancer cells. Our results indicate a dependence on glycolysis despite different glycolytic ATP levels in all cancer cell lines tested. In addition, our data show that high levels of ROS in TN cells are a result of limited antioxidant capacity in the NADPH producing and GSH systems, mitochondrial dysfunction and non-mitochondrial ROS production, making them more sensitive to GSH synthesis inhibitors. Our data suggest that metabolic and antioxidant profiling of breast cancer will provide important targets for metabolic inhibitors or antioxidant treatments for breast cancer therapy.

Isolation and Identification of Arsenic-Resistant Extremophilic Bacteria from the Crater-Lake Volcano "El Chichon", Mexico.

The crater lake at "El Chichón" volcano is an extreme acid-thermal environment with high concentrations of heavy metals. In this study, two bacterial strains with the ability to resist high concentrations of arsenic (As) were isolated from water samples from the crater lake. Staphylococcus ARSC1-P and Stenotrophomonas ARSC2-V isolates were identified by use of the 16S rDNA gene. Staphylococcus ARSC1-P was able to grow in 400 mM of arsenate [As(V)] under oxic and anoxic conditions. The IC50 values were 36 and 382 mM for oxic and anoxic conditions, respectively. For its part, Stenotrophomonas ARSC2-V showed IC50 values of 110 mM and 2.15 for As(V) and arsenite [As(III)], respectively. Arsenic accumulated intracellularly in both species [11-25 nmol As × mg cellular prot-1 in cells cultured in 50 mM As(V)]. The present study shows evidence of microbes that can potentially be a resource for the bio-treatment of arsenic in contaminated sites, which highlights the importance of the "El Chichón" volcano as a source of bacterial strains that are adaptable to extreme conditions.

Metagenomic and metabolic analyses of poly-extreme microbiome from an active crater volcano lake.

El Chichón volcano is one of the most active volcanoes in Mexico. Previous studies have described its poly-extreme conditions and its bacterial composition, although the functional features of the complete microbiome have not been characterized yet. By using metabarcoding analysis, metagenomics, metabolomics and enzymology techniques, the microbiome of the crater lake was characterized in this study. New information is provided on the taxonomic and functional diversity of the representative Archaea phyla, Crenarchaeota and Euryarchaeota, as well as those that are representative of Bacteria, Thermotogales and Aquificae. With culture of microbial consortia and with the genetic information collected from the natural environment sampling, metabolic interactions were identified between prokaryotes, which can withstand multiple extreme conditions. The existence of a close relationship between the biogeochemical cycles of carbon and sulfur in an active volcano has been proposed, while the relationship in the energy metabolism of thermoacidophilic bacteria and archaea in this multi-extreme environment was biochemically revealed for the first time. These findings contribute towards understanding microbial metabolism under extreme conditions, and provide potential knowledge pertaining to "microbial dark matter", which can be applied to biotechnological processes and evolutionary studies.