RESUMEN
Black hair-salon workers face serious health hazards from the product they use on clients and other health hazards at their work. Currently there is a significant research gap in understanding the prevalence of workplace related exposures and health outcomes. The primary objective of this study was to gather preliminary data on workplace exposures and health outcomes of hair care workers in South Los Angeles. We conducted 22 surveys of salon workers at 16 salons. The results suggest the need for proper health and safety training within the salon worker community, specifically around chemical hair services. The results also suggest ergonomic workstation assessments and recommendations would be beneficial to reduce musculoskeletal disorders. Willingness of stylists to learn more about workplace hazards and how to mitigate their risks was high. Our findings indicate the need for a larger community based participatory research study on the workplace exposures of Black salon workers.
Asunto(s)
Industria de la Belleza , Investigación Participativa Basada en la Comunidad , Encuestas Epidemiológicas , Salud Laboral , Adulto , Femenino , Humanos , Los Angeles , Masculino , Persona de Mediana Edad , Exposición ProfesionalRESUMEN
Ten p-nitrodiarylthiourea analogs were designed, synthesized and evaluated in breast (MCF-7, T-47D, MDA-MB-453) and prostate (DU-145, PC-3, LNCaP) cancer cell lines for their anticancer activities. The majority of the compounds were able to inhibit the growth of these six cancer cell lines at low micromolar concentrations. Compound 7 was found to be the most potent anticancer agent in this series with GI50 values of 3.16µM for MCF-7, 2.53µM for T-47D, 4.77µM for MDA-MB-453 breast cancer lines and 3.54µM for LNCaP prostate cancer cell line. These GI50 values were comparable to the parent compound, SHetA2.
Asunto(s)
Antineoplásicos/síntesis química , Tiourea/química , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Humanos , Células MCF-7 , Relación Estructura-Actividad , Tiourea/síntesis química , Tiourea/farmacologíaRESUMEN
Cadmium is an environmental carcinogen that usually enters the body at minute concentrations through diet or cigarette smoke and bioaccumulates in soft tissues. In past studies, cadmium has been shown to contribute to the development of more aggressive cancer phenotypes including increased cell migration and invasion. This study aims to determine if cadmium exposure-both acute and chronic-contributes to breast cancer progression by interfering with the normal functional relationship between E-cadherin and ß-catenin. An MCF7 breast cancer cell line (MCF7-Cd) chronically exposed to 10(-7) M CdCl2 was previously developed and used as a model system to study chronic exposures, whereas parental MCF7 cells exposed to 10(-6) M CdCl2 for short periods of time were used to study acute exposures. Cadmium exposure of MCF7 cells led to the degradation of the E-cadherin protein via the ubiquitination pathway. This resulted in fewer E-cadherin/ß-catenin complexes and the relocation of active ß-catenin to the nucleus, where it interacted with transcription factor TCF-4 to modulate gene expression. Interestingly, only cells chronically exposed to cadmium showed a significant decrease in the localization of ß-catenin to the plasma membrane and an increased distance between cells. Our data suggest that cadmium exposure promotes breast cancer progression by (1) down-regulating E-cadherin, thus decreasing the number of E-cadherin/ß-catenin adhesion complexes, and (2) enhancing the nuclear translocation of ß-catenin to increase expression of cancer-promoting proteins (i.e., c-Jun and cyclin D1).
Asunto(s)
Neoplasias de la Mama/metabolismo , Cadherinas/metabolismo , Cadmio/efectos adversos , Proteolisis/efectos de los fármacos , Factores de Transcripción Básicos con Cremalleras de Leucinas y Motivos Hélice-Asa-Hélice/metabolismo , Neoplasias de la Mama/patología , Línea Celular Tumoral , Núcleo Celular/efectos de los fármacos , Núcleo Celular/metabolismo , Progresión de la Enfermedad , Regulación hacia Abajo/efectos de los fármacos , Femenino , Expresión Génica/efectos de los fármacos , Humanos , Células MCF-7 , Factor de Transcripción 4 , Factores de Transcripción/metabolismo , Ubiquitinación/efectos de los fármacos , beta Catenina/metabolismoRESUMEN
Cadmium is a metalloestrogen known to activate the estrogen receptor and promote breast cancer cell growth. Previous studies have implicated cadmium in the development of more malignant tumors; however the molecular mechanisms behind this cadmium-induced malignancy remain elusive. Using clonal cell lines derived from exposing breast cancer cells to cadmium for over 6 months (MCF-7-Cd4, -Cd6, -Cd7, -Cd8 and -Cd12), this study aims to identify gene expression signatures associated with chronic cadmium exposure. Our results demonstrate that prolonged cadmium exposure does not merely result in the deregulation of genes but actually leads to a distinctive expression profile. The genes deregulated in cadmium-exposed cells are involved in multiple biological processes (i.e. cell growth, apoptosis, etc.) and molecular functions (i.e. cadmium/metal ion binding, transcription factor activity, etc.). Hierarchical clustering demonstrates that the five clonal cadmium cell lines share a common gene expression signature of breast cancer associated genes, clearly differentiating control cells from cadmium exposed cells. The results presented in this study offer insights into the cellular and molecular impacts of cadmium on breast cancer and emphasize the importance of studying chronic cadmium exposure as one possible mechanism of promoting breast cancer progression.
Asunto(s)
Cadmio/toxicidad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Células MCF-7/efectos de los fármacos , Análisis por Conglomerados , Cartilla de ADN/genética , Femenino , Perfilación de la Expresión Génica/métodos , Humanos , Análisis por Micromatrices , Reacción en Cadena de la Polimerasa de Transcriptasa InversaRESUMEN
Cadmium is an omnipotent environmental contaminant associated with the development of breast cancer. Studies suggest that cadmium functions as an endocrine disruptor, mimicking the actions of estrogen in breast cancer cells and activating the receptor to promote cell growth. Although acute cadmium exposure is known to promote estrogen receptor-mediated gene expression associated with growth, the consequence of chronic cadmium exposure is unclear. Since heavy metals are known to bioaccumulate, it is necessary to understand the effects of prolonged cadmium exposure. This study aims to investigate the effects of chronic cadmium exposure on breast cancer progression. A MCF7 breast cancer cell line chronically exposed to 10(-7) M CdCl2 serves as our model system. Data suggest that prolonged cadmium exposures result in the development of more aggressive cancer phenotypes - increased cell growth, migration and invasion. The results from this study show for the first time that chronic cadmium exposure stimulates the expression of SDF-1 by altering the molecular interactions between ERα, c-jun and c-fos. This study provides a mechanistic link between chronic cadmium exposure and ERα and demonstrates that prolonged, low-level cadmium exposure contributes to breast cancer progression.
Asunto(s)
Neoplasias de la Mama/metabolismo , Cadmio/toxicidad , Quimiocina CXCL12/biosíntesis , Receptor alfa de Estrógeno/metabolismo , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Neoplasias de la Mama/patología , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Proliferación Celular/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Invasividad Neoplásica , Proteínas Proto-Oncogénicas c-fos/metabolismo , Proteínas Proto-Oncogénicas c-jun/metabolismoRESUMEN
Prostanoids play an important role in a variety of physiological and pathophysiological processes including inflammation and cancer. The rate-limiting step in the prostanoid biosynthesis pathway is catalyzed by cyclooxygenase-2 (COX-2). COX-2 exists as two glycoforms, 72 and 74 kDa, the latter resulting from an additional glycosylation at Asn(580). In this study, Asn(580) was mutated, and the mutant and wild-type COX-2 genes were expressed in COS-1 cells to determine how glycosylation affects the inhibition of COX-2 activity by aspirin, flurbiprofen, ibuprofen, celecoxib, and etoricoxib. Results indicate that certain inhibitors were 2-5 times more effective at inhibiting COX-2 activity when the glycosylation site was eliminated, indicating that glycosylation of COX-2 at Asn(580) decreases the efficacy of some inhibitors.