Marine Animal-Derived Compounds and Autophagy Modulation in Breast Cancer Cells

It is known that in breast cancer biology, autophagy mainly plays a cytoprotective and anti-apoptotic role in vitro, being conceivably responsible for cell resistance to drug exposure and a higher metastatic attitude in vivo. Thus, the development of novel autophagy-targeting agents represents a valuable strategy to improve the efficacy of anticancer interventions. It is widely acknowledged that the enormous biodiversity of marine organisms represents a highly promising reserve for the isolation of bioactive primary and secondary metabolites targeting one or several specific molecular pathways and displaying active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of marine animal-derived extracts or isolated compounds which exert a modulatory effect on the autophagic process in breast cancer cells and list them with respect to the taxonomical hierarchy of the producing species. Where available, the molecular and biochemical aspects associated with the molecules or extracts under discussion will be also summarized

electrophoresis of unlabeled proteins in a sequencing gel apparatus

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Cadmium-Associated Molecular Signatures in Cancer Cell Models

The exposure of cancer cells to cadmium and its compounds is often associated with the development of more malignant phenotypes, thereby contributing to the acceleration of tumor progression. It is known that cadmium is a transcriptional regulator that induces molecular reprogramming, and therefore the study of differentially expressed genes has enabled the identification and classification of molecular signatures inherent in human neoplastic cells upon cadmium exposure as useful biomarkers that are potentially transferable to clinical research. This review recapitulates selected studies that report the detection of cadmium-associated signatures in breast, gastric, colon, liver, lung, and nasopharyngeal tumor cell models, as specifically demonstrated by individual gene or whole genome expression profiling. Where available, the molecular, biochemical, and/or physiological aspects associated with the targeted gene activation or silencing in the discussed cell models are also outlined

Cytogenetic characterization of HB2 epithelial cells from the human breast

HB2 is a cell line originated by subcloning of MTSV1-7 mammary luminal epithelial cells isolated from human milk and immortalization via introduction of the gene encoding simian virus 40 (SV40) large T antigen. Despite its wide utilization as non-neoplastic counterpart in assays aimed to elucidating various biochemical and genetical aspects of normal and tumoral breast cells, to our knowledge no literature data have so far appeared concerning the chromosomal characterization of the HB2 cells. Here, we report the cytogenetic characterization of the karyotype of HB2 cells, which puts in evidence the occurrence of changes in chromosomal number and structure and the presence of unidentified chromosomal markers in variable amount. Our results do not detract from the utility of HB2 cells in illustrating fundamental aspects of breast cell biology, but rather interject a note of caution into generalizing results obtained with this cell line to other non-immortalized epithelial cell populations from the human breast. Therefore, this work represents a useful resource for all who want to perform appropriate and focused future studies on this cell line and proposes precise indications for a knowledgeable use of HB2 cells

Effect of transfection with PLP2 antisense oligonucleotides on gene expression of cadmium-treated MDA-MB231 breast cancer cells

Emerging evidence indicates that cadmium (Cd) is able to regulate gene expression, drastically affecting the pattern of transcriptional activity in human normal and pathological cells. We have already shown that exposure of MDA-MB231 breast cancer cells to 5 uM CdCl2 for 96 h, apart from affecting significantly mitochondrial metabolism, induces modifications of the expression level of genes coding for members of stress response-, mitochondrial respiration-, MAP kinase-, NF-kB and apoptosis-related pathways. In the present study, we have expanded the knowledge on the biological effects of Cd-breast cancer cell interactions, indicating PLP2 (proteolipid protein-2) as a novel member of the list of Cd-upregulated genes by MDA-MB231 cancer cells and, through the application of transfection techniques with specific antisense oligonucleotides, we have demonstrated that such over-expression may be an upstream event to some of the changes of gene expression levels already observed in Cd-treated cells, thus unveiling new possible molecular relationship between PLP2 and genes linked to the stress- and apoptotic responses

Cytotoxicity of the urokinase-plasminogen activator inhibitor carbamimidothioic acid (4-boronophenyl) methyl ester hydrobromide (BC-11) on triple-negative MDA-MB231 breast cancer cells

Abstract: BC-11 is an easily synthesized simple thiouronium-substituted phenylboronic acid, which has been shown to be cytotoxic on triple negative MDA-MB231 breast cancer cells by inducing a perturbation of cell cycle when administered at a concentration equal to its ED50 at 72 h (117 μM). Exposure of cells to BC-11, either pre-absorbed with a soluble preparation of the N-terminal fragment of urokinase-plasminogen activator (uPa), or in co-treatment with two different EGFR inhibitors, indicated that: (i) BC-11 acts via binding to the N-terminus of the enzyme where uPa- and EGF receptor-recognizing sites are present, thereby abrogating the growth-sustaining effect resulting from receptor binding; and (ii) the co-presence of the EGFR inhibitor PD153035 potentiates BC-11’s cytotoxicity. Exposure of cells to a higher concentration of BC-11 corresponding to its ED75 at 72 h (250 μM) caused additional impairment of mitochondrial activity, the production of reactive oxygen species and promotion of apoptosis. Therefore, BC-11 treatment appears to show potential for the development of this class of compounds in the prevention and/or therapy of “aggressive” breast carcinoma

Collective locomotion of human cells, woundh healing and their control by extracts and isolated compounds from marine ivertebrates

The collective migration of cells is a complex integrated process that represents a common theme joining morphogenesis, tissue regeneration, and tumor biology. It is known that a remarkable amount of secondary metabolites produced by aquatic invertebrates displays active pharmacological properties against a variety of diseases. The aim of this review is to pick up selected studies that report the extraction and identification of crude extracts or isolated compounds that exert a modulatory effect on collective cell locomotion and/or skin tissue reconstitution and recapitulate the molecular, biochemical, and/or physiological aspects, where available, which are associated to the substances under examination, grouping the producing species according to their taxonomic hierarchy. Taken all of the collected data into account, marine invertebrates emerge as a still poorly-exploited valuable resource of natural products that may significantly improve the process of skin regeneration and restrain tumor cell migration, as documented by in vitro and in vivo studies. Therefore, the identification of the most promising invertebrate-derived extracts/molecules for the utilization as new targets for biomedical translation merits further and more detailed investigations

Science and Healthy Meals in the World: Nutritional Epigenomics and Nutrigenetics of the Mediterranean Diet

The Mediterranean Diet (MD), UNESCO Intangible Cultural Heritage of Humanity, has become a scientific topic of high interest due to its health benefits. The aim of this review is to pick up selected studies that report nutrigenomic or nutrigenetic data and recapitulate some of the biochemical/genomic/genetic aspects involved in the positive health effects of the MD. These include (i) the antioxidative potential of its constituents with protective effects against several diseases; (ii) the epigenetic and epigenomic effects exerted by food components, such as Indacaxanthin, Sulforaphane, and 3-Hydroxytyrosol among others, and their involvement in the modulation of miRNA expression; (iii) the existence of predisposing or protective human genotypes due to allelic diversities and the impact of the MD on disease risk. A part of the review is dedicated to the nutrigenomic effects of the main cooking methods used in the MD and also to a comparative analysis of the nutrigenomic properties of the MD and other diet regimens and non-MD-related aliments. Taking all the data into account, the traditional MD emerges as a diet with a high antioxidant and nutrigenomic modulation power, which is an example of the "Environment-Livings-Environment" relationship and an excellent patchwork of interconnected biological actions working toward human health

Effects of cadmium chloride on some mitochondria-related activity and gene expression of human MDA-MB231 breast tumor cells

It was reported that cadmium is able to exert a cytotoxic effect on tumor MDA-MB231 cells, which shows signs of "non-classical" apoptosis and is characterized by drastic changes in gene expression pattern. In this study, we have extended our knowledge of metal-breast cancer cell interactions by analyzing some mitochondria-related aspects of the stress response to CdCl(2) at either 5 or 50 microM 24- or 96-h exposure, by cytochemical, conventional PCR and Northern/Western blot techniques. We demonstrated that (i) no modification of the mitochondrial mass was detectable due to CdCl(2) exposure; (ii) the respiration activity appeared to be increased after 96-h exposures, while the production of reactive oxygen species was significantly induced, as well; (iii) hsp60, hsp70, COXII and COXIV expressions were dependent on the duration of Cd exposure; (iv) a different hsp60 protein distribution was observed in mitochondrial and post-mitochondrial extracts and (v) 96-h exposure induced the over-expression of hsc/hsp70 proteins and, conversely, the down-regulation of cytochrome oxidase subunits II and IV. These observations, in addition to providing more information on the cellular and molecular aspects of the interaction between CdCl(2) and MDA-MB231 breast tumor cells, contribute to the comprehension of the intracellular molecular mechanisms implicated in the regulation of some mitochondrial proteins