Estrogen Induced Metastatic Modulators MMP-2 and MMP-9 Are Targets of 3,3′-Diindolylmethane in Thyroid Cancer

Thyroid cancer is the most common endocrine related cancer with increasing incidences during the past five years. Current treatments for thyroid cancer, such as surgery or radioactive iodine therapy, often require patients to be on lifelong thyroid hormone replacement therapy and given the significant recurrence rates of thyroid cancer, new preventive modalities are needed. The present study investigates the property of a natural dietary compound found in cruciferous vegetables, 3,3'-diindolylmethane (DIM), to target the metastatic phenotype of thyroid cancer cells through a functional estrogen receptor.Thyroid cancer cell lines were treated with estrogen and/or DIM and subjected to in vitro adhesion, migration and invasion assays to investigate the anti-metastatic and anti-estrogenic effects of DIM. We observed that DIM inhibits estrogen mediated increase in thyroid cell migration, adhesion and invasion, which is also supported by ER-α downregulation (siRNA) studies. Western blot and zymography analyses provided direct evidence for this DIM mediated inhibition of E(2) enhanced metastasis associated events by virtue of targeting essential proteolytic enzymes, namely MMP-2 and MMP-9.Our data reports for the first time that DIM displays anti-estrogenic like activity by inhibiting estradiol enhanced thyroid cancer cell proliferation and in vitro metastasis associated events, namely adhesion, migration and invasion. Most significantly, MMP-2 and MMP-9, which are known to promote and enhance metastasis, were determined to be targets of DIM. This anti-estrogen like property of DIM may lead to the development of a novel preventive and/or therapeutic dietary supplement for thyroid cancer patients by targeting progression of the disease

Impact of sediment type, light and nutrient availability on benthic diatom communities of a large estuarine bay: Moreton Bay, Australia

Shifts in diatom species composition may be used to infer past changes in environmental conditions in fresh, estuarine and marine systems. Establishing the primary drivers of present day diatom community composition is a vital step in their use as a proxy for past conditions. Moreton Bay, Australia, has experienced extensive modification of its catchments and western and southern shorelines. Regional weather patterns and terrestrial runoff have created a gradient in water quality from relatively degraded western and southern areas to relatively pristine northern and eastern areas. The aim of this study was to examine the relative impact of short term changes to light and/or nutrient availability and long term changes in sediment type, light and nutrient availability to subtidal benthic community composition. Short term changes were imposed using a manipulative field experiment whilst long term changes were obtained from a field survey of sites across the gradient of water quality. Diatoms were found to be the dominant microalgal group at all studied sites. The diatom communities were comprised primarily of small benthic epipsammic species and community composition was primarily driven by changes in sediment silt content. Short term changes in light and/or nutrient availability had little impact on community composition. In this open estuarine system the use of diatom indices to infer past water quality must take into account the sediment silt content in their interpretations