bioRxiv Science⌕ Search

bioRxiv · 10.1101/2024.11.08.622500

Hydrocarbon effects on cell survival and antioxidant system of breast tumorigenic and non-tumorigenic cells.

Abstract

Over the last decades, environmental pollution with polycyclic aromatic hydrocarbons (PAH) has risen due to human development and industrial activities. The consequences of potential contamination with oil or any of its components must be evaluated. Here, we faced the effects on cell growth and detoxification that might arise from the exposure to hydrocarbons sourced from contaminated waters. MCF-7 and MDA-MB-231 human breast cancer cells and/or MCF-10A epithelial non-tumorigenic cells were exposed to water-accommodated oil fraction (WAF) or anthracene as a PAH currently found in the environment to evaluate clonogenicity, viability, GST and CAT activities. WAF decreased MDA-MB-231 cells clonogenicity and MDA-MB-231 and MCF-7 cells viability. Anthracene significantly reduced non-tumorigenic cells viability and clonogenicity, without affecting the survival of tumorigenic cells. Both tumorigenic cells responded mainly by activating the antioxidant system through the increment of CAT when exposed to low concentrations of WAF. In both cell lines, WAF also increased GST. Anthracene exposure significantly decreased CAT activity of the three cell lines evaluated. GST activity decreased 38% after 28 {micro}M anthracene exposure in MDA-MB-231 cells (p<0.05) and 15, 17 and 21% after 7 (p<0.05), 14 and 28 {micro}M (p<0.01) in MCF-10A cells, while in MCF-7 cells 28 {micro}M anthracene increased GST activity by 75% (p<0.001). We conclude that the sensitivity of cells to the different contaminants evaluated is affected by the degree of cellular tumorigenicity and exposure to WAF or anthracene may exacerbate malignant conditions. The integration of multiple parameters, analyzed through multivariate methods, offers a comprehensive evaluation of toxicant effects. HIGHLIGHTSO_LIWAF and anthracene affect tumorigenic mammary cells viability and clonogenicity C_LIO_LINon tumorigenic mammary cells show more sensitivity to anthracene exposure C_LIO_LIWAF activates antioxidant and detoxicant system in tumorigenic mammary cells C_LIO_LIAnthracene decreased CAT activity of tumorigenic and non-tumorigenic mammary cells C_LIO_LIAnthracene affected GST activity of tumorigenic and non-tumorigenic mammary cells C_LI

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

Mardirosian, M. N., Lasagna, M., Nunez, M., Galarza, T., Espert, N., Venturino, A., Cocca, C.. 2024-11-10. Hydrocarbon effects on cell survival and antioxidant system of breast tumorigenic and non-tumorigenic cells.. https://doi.org/10.1101/2024.11.08.622500

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related preprints

Differential requirement for the Ire1 luminal domain in Candida albicans drug susceptibility and pathogenicity

The opportunistic human pathogen Candida albicans depends on the unfolded protein response (UPR) for cell wall integrity, antifungal tolerance, filamentous growth, and virulence. The UPR is driven by the conserved transmembrane sensor Ire1, which is activated either by misfolded proteins through its luminal domain or by lipid bilayer stress (LBS) through its transmembrane domain. In budding yeast, these two activation modes deploy divergent transcriptional programs. Whether the requirement for these two input domains is separable in C. albicans, where the cell membrane and cell wall are themselves the targets of major antifungal drug classes, remains unknown. Here, we engineered a C. albicans strain expressing Ire1 lacking an intact luminal domain (ire1{Delta}LD), which no longer detects proteotoxic stress. The ire1{Delta}LD strain grew in the presence of the azole antifungals fluconazole and miconazole but was highly sensitive to heat shock, cell wall stress, and the echinocandin caspofungin. It was also unable to sustain filamentous growth and showed reduced virulence in a Caenorhabditis elegans infection model. RNA sequencing revealed only modest changes to the steady-state transcriptome of ire1{Delta}LD cells. Together, these findings define a differential requirement for the input domains of C. albicans Ire1, uncoupling growth under azole-induced membrane stress from the cell wall, thermal, and virulence-associated outputs that depend on proteotoxic sensing, a distinction that could inform antifungal strategies targeting the UPR.

cell biology↗

Nucleosome Core Allostery Governs Chromatin Recognition and Cell Fate

Nucleosomes regulate chromatin folding, accessibility, and factor recruitment. Current models primarily attribute these functions to histone tail modifications, while the core is largely viewed as a structural scaffold. Yet subtle changes within the nucleosome core can produce profound functional consequences, and the mechanisms underlying these effects remain unclear. Here, we describe nucleosome core allostery as a fundamental principle of chromatin regulation that amplifies the impact of minimal nucleosome variations. Leveraging natural differences between H2A.Z variants, we show that the nucleosome core encodes distinct conformational dynamics that propagate allosterically, thereby controlling nucleosome accessibility and recognition by chromatin factors. As a result, a single buried amino acid substitution alone is sufficient to reprogram nucleosome dynamics and bias cell identity. Our findings establish the nucleosome core as an allosteric regulatory module and provide a generalizable framework for how subtle variation within nucleosomes is amplified into diverse biological outcomes in development and disease.

cell biology↗

YAP/TAZ-controlled ERK dynamics coordinate progenitor expansion and differentiation commitment

Progenitor cells must proliferate to expand the cell population, yet terminal differentiation requires this proliferative state to end. How signaling controls the duration of this proliferative window remains poorly understood. Using adipogenesis and live single-cell imaging of differentiation, cell-cycle, and ERK-activity reporters, we show that YAP and TAZ coordinate progenitor expansion with differentiation commitment by regulating ERK dynamics. YAP/TAZ maintain cells in a fluctuating high-ERK state that promotes proliferation while actively keeping the differentiation driver PPARG below the threshold for irreversible commitment. Crucially, this differentiation block is not explained by proliferation alone: inhibiting CDK4/6 or AKT suppressed proliferation without restoring differentiation, whereas MEK-ERK inhibition restored differentiation even when YAP/TAZ activity remained high. As YAP/TAZ activity decreases, dampened ERK fluctuations trigger PPARG activation. These findings support a self-limiting model in which YAP/TAZ-driven progenitor expansion progressively increases cell density and contact-dependent Hippo signaling, reducing YAP/TAZ activity and terminating the proliferative phase. Consequently, transient YAP/TAZ activation expands the progenitor pool while preserving subsequent differentiation, whereas sustained activation suppresses commitment. Together, these findings identify YAP/TAZ-controlled ERK dynamics as the nexus coordinating progenitor expansion with terminal differentiation and suggest that slower density-dependent Hippo feedback may set the duration of this proliferative window to regulate differentiated cell-number output.

cell biology↗