Biology subjects

Cocca, C.

Publications and source records attributed to Cocca, C..

3 recordsLinked to original sources

bioRxiv2025

Chlorpyrifos and tamoxifen co-pretreatment promotes stem-like phenotype and upregulation of anti-estrogen therapy resistance markers in ERα breast cancer cells

Endocrine therapy (ET) is the standard first-line treatment for hormone receptor positive breast cancer but about 30% of patients develop resistance. Chlorpyrifos (CPF), is an endocrine disruptor pesticide that promotes a stemness phenotype and triggers molecular mechanisms involved in ET resistance. The goal of this study is to assess whether CPF induces tamoxifen (TAM) resistance by modulating estrogen receptor alpha (RE) expression through histone deacetylase 1 (HDAC1) regulation. We analyzed public databases of breast cancer patients and performed in vitro experiments using the MCF-7 cell line. We evaluated whether the co-pretreatment with CPF and TAM (CPF+TAM) modulates stemness and ET resistance markers. We found that CPF+TAM selects cells that exhibit increased clonogenicity, enhanced mammosphere-forming ability, and upregulates the stemness markers CD44, NANOG and POU5F1 while decreasing CD24. This selected cell subpopulation shows higher levels of mRNA and elevated protein expression of RE and HDAC1. Finally, we identified a resistance and stemness marker signature induced by CPF+TAM that closely resembles the profile observed in the dataset of patients who acquired tamoxifen resistance. Our findings show that CPF promotes an undifferentiated basal-like cell phenotype that contributes to TAM resistance, reinforcing the need for global restrictions to safeguard public health.

cancer biology↗

bioRxiv2024

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

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

cell biology↗

bioRxiv2024

Chlorpyrifos induces lung metastases and modulation of cancer stem cell markers in triple negative breast cancer model

Breast cancer is a major public health problem, and distant metastases are the main cause of morbidity and mortality. Chlorpyrifos is an organophosphate that promotes Epithelial-Mesenchymal Transition-like phenotype in breast cancer cell lines and modulates the Breast Cancer Stem Cells activating two key processes related to the metastatic cascade. Here, we investigated whether Chlorpyrifos may induce distant metastases in an in vivo triple negative tumor model. Also, we studied the expression of Breast Cancer Stem Cell and Epithelial-Mesenchymal Transition activation-markers in Triple Negative Breast Cancer mice tumors and human cells. We demonstrate that Chlorpyrifos modulates stem cell plasticity as a function of growth conditions in monolayer or three-dimensional culture. Furthermore, Chlorpyrifos decreased the doubling period, increased tumor volume, stimulated the infiltration of adjacent muscle fibers and induced lung metastases in mice. Finally, Chlorpyrifos modulated the expression of Epithelial-Mesenchymal Transition and BCSC markers in mice exposed to the pesticide. All our findings confirm that Chlorpyrifos promotes breast cancer progression, enhances stemness and Epithelial-Mesenchymal Transition marker expression and generates lung metastases in an in vivo model induced in mice.

cancer biology↗