RESUMO
A policy mandating the completion of an online learning module for healthcare workers intending to decline influenza immunization was associated with a nearly 25% relative increase in immunization and significant reduction in healthcare-associated influenza. In the absence of mandatory vaccination, this model may help to augment severe acute respiratory coronavirus virus 2 (SARS-CoV-2) vaccine efforts.
RESUMO
In this study, we determined the effect of low dose piperlongumine on the motility/invasive capacity and epithelial-to-mesenchymal transition (EMT) of MDA-MB-231 triple-negative breast cancer (TNBC) cells and the metastasis of 4T1 mouse mammary carcinoma cells. MTT assays measured the effect of piperlongumine on TNBC cell growth. Motility/invasiveness were determined by gap closure/transwell assays. Western blotting assessed ZEB1, Slug, and matrix metalloproteinase (MMP) 9 expression. Interleukin (IL) 6 was detected by ELISA. MMP2, E-cadherin, and miR-200c expression was determined by real-time quantitative polymerase chain reaction. Reactive oxygen species (ROS) were measured by flow cytometry. The orthotopic 4T1 mouse model of breast cancer was used to examine metastasis. Piperlongumine-treated MDA-MB-231 cells showed reduced motility/invasiveness, decreased MMP2 and MMP9 expression, increased miR-200c expression, reduced IL-6 synthesis, decreased expression of ZEB1 and Slug, increased E-cadherin expression, and epithelial-like morphology. Piperlongumine also inhibited transforming growth factor ß-induced ZEB1 and Slug expression. ROS accumulated in piperlongumine-treated cells, while changes in metastasis-associated gene expression were ablated by exogenous glutathione. Metastasis of 4T1 cells to the lungs of BALB/c mice was dramatically reduced in piperlongumine-treated animals. These findings reveal a previously unknown capacity of low dose piperlongumine to interfere with TNBC metastasis via an oxidative stress-dependent mechanism.
Assuntos
Alcaloides , Carcinoma , Neoplasias de Mama Triplo Negativas , Alcaloides/farmacologia , Animais , Linhagem Celular Tumoral , Movimento Celular , Dioxolanos , Transição Epitelial-Mesenquimal , Regulação Neoplásica da Expressão Gênica , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Neoplasias de Mama Triplo Negativas/metabolismoRESUMO
Epidemiological studies show that fruit- and vegetable-rich diets are associated with a reduced risk of developing certain forms of cancer, including breast cancer. In this study we demonstrate that a subcytotoxic concentration of apigenin, which is a flavone found at high concentrations in parsley, onions, grapefruit, oranges, and chamomile tea, inhibited DNA synthesis in a panel of human breast cancer cell lines (MDA-MB-231, MBA-MB-468, MCF-7, SK-BR-3). Decreased proliferation of MDA-MB-468 cells in the presence of apigenin was associated with G2/M phase cell cycle arrest and the production of reactive oxygen species. Apigenin-treated MDA-MB-468 cells also showed reduced phosphorylation of Akt (protein kinase B), which is an essential effector serine/threonine kinase in the phosphatidylinositide 3-kinase pathway that promotes tumor growth and progression. However, exposure to the antioxidant reduced glutathione failed to reverse apigenin-mediated inhibition of Akt phosphorylation and cell proliferation, indicating that these effects were not due to oxidative stress. Taken together, these findings suggest that low-dose apigenin has the potential to slow or prevent breast cancer progression.