Selenium - its role in physiology and endocrinology and as organoselenium compounds in oncology: A minireview.

The present minireview traces the road leading to discovery of selenium, formerly appointed as a toxic element that became later a bioelement, which is necessary for the proper functioning of living organisms. Selenium occurs in human and animal bodies either in the form of seleno-Lcysteine or its dimeric form seleno-L-cystine as a crucial component of selenoenzymes or selenoproteins. Selenium atom represents an integral component of the enzyme active site of different forms of glutathione peroxidase, which catalyzes conversion of hydrogen peroxide and organic hydroperoxides into the water and corresponding alcohols.

Triphenyltin isoselenocyanate: a novel nuclear retinoid X receptor ligand with antiproliferative and cytotoxic properties in cell lines derived from human breast cancer.

Several commercially available triorganotin compounds were previously found to function as agonist ligands for nuclear retinoid X receptor (RXR) molecules. Triphenyltin isoselenocyanate (TPT-NCSe), a novel selenium atom containing a derivative of triorganotin origin, was found to represent a new cognate bioactive ligand for RXRs. TPT-NCSe displayed a concentration- and time-dependent decrease in the cell viability in both human breast carcinoma MCF-7 (estrogen receptor positive) and MDA‑MB‑231 (triple negative) cell lines.

Biological functions of kojic acid and its derivatives in medicine, cosmetics, and food industry: Insights into health aspects.

This review traces the road leading to the demonstration of a variety of kojic acid chemical and biological properties. It illustrates the biological effects of several synthetic kojic acid derivatives. Besides the main capability of kojic acid to inhibit the activity of tyrosinase in melanin synthesis, the focus is also on antibacterial, antifungal, antiproliferative, anti-inflammatory, and other biological activities of kojic acid derivatives, which may be applicable in medicine.

In vitro antiproliferative and cytotoxic activities of novel triphenyltin isoselenocyanate in human breast carcinoma cell lines MCF 7 and MDA-MB-231.

Intensive investigation for novel antiproliferative and cytotoxic effective chemical compounds is currently concentrated on structurally modified agents of natural or synthetic source. The selenium derivative of triorganotin compound, triphenyltin isoselenocyanate (TPT-NCSe) caused higher cytotoxicity in hormone sensitive MCF 7 (IC 50-250 nM) in comparison with triple-negative MDA-MB-231 breast carcinoma cell line (IC 50-450 nM) as determined by MTT assay. Measurement of DNA damage showed presence of crosslinks in both cell lines treated by increasing TPT-NCSe concentrations.

The effect of all-trans retinoic acid on the mitochondrial function and survival of cardiomyoblasts exposed to local photodamage.

Using H9C2 cardiomyoblasts, we have shown that all-trans retinoic acid (ATRA), the biologically active metabolite of vitamin A, affects mitochondrial dynamics and functions. The low dose (10 nM) ATRA stimulates the expression of nuclear retinoid receptors and induces mechanisms that are protective against severe local damage caused by laser irradiation at the mitochondrial level. These changes include increased density of the mitochondrial network, higher number of mitochondrial junctions, and enhanced mitochondrial velocity.

Thyroid hormone and thyroid hormone nuclear receptors: History and present state of art.

The present review traces the road leading to discovery of L-thyroxine, thyroid hormone (3,5,3´-triiodo-L-thyronine, T) and its cognate nuclear receptors. Thyroid hormone is a pleio-tropic regulator of growth, differentiation, and tissue homeostasis in higher organisms. The major site of the thyroid hormone action is predominantly a cell nucleus.

Natural and synthetic retinoid X receptor ligands and their role in selected nuclear receptor action.

Important key players in the regulatory machinery within the cells are nuclear retinoid X receptors (RXRs), which compose heterodimers in company with several diverse nuclear receptors, playing a role as ligand inducible transcription factors. In general, nuclear receptors are ligand-activated, transcription-modulating proteins affecting transcriptional responses in target genes. RXR molecules forming permissive heterodimers with disparate nuclear receptors comprise peroxisome proliferator-activated receptors (PPARs), liver X receptors (LXRs), farnesoid X receptor (FXR), pregnane X receptor (PXR) and constitutive androstan receptor (CAR).

CD44 and vimentin, markers involved with epithelial-mesenchymal transition: A proteomic analysis of sequential proteins extraction of triple-negative breast cancer cells after treatment with all-trans retinoic acid.

This work aimed to provide, in one isolation and separation step, an overview of the content of proteins with different solubility after treatment with all-trans retinoic acid, which is considered to be an important therapeutic agent, predominantly in acute promyelocytic leukemia. Breast, ovarian, bladder, and skin cancers have been demonstrated to be suppressed by retinoic acid, as well. The bottom-up proteomic strategies were applied for the analysis of proteins extracted from triple-negative breast cancer MDA-MB-231 cells utilizing a commercially manufactured kit.

Targeting the pregnane X receptor using microbial metabolite mimicry.

The human PXR (pregnane X receptor), a master regulator of drug metabolism, has essential roles in intestinal homeostasis and abrogating inflammation. Existing PXR ligands have substantial off-target toxicity. Based on prior work that established microbial (indole) metabolites as PXR ligands, we proposed microbial metabolite mimicry as a novel strategy for drug discovery that allows exploiting previously unexplored parts of chemical space.

Down-regulation of vimentin by triorganotin isothiocyanates-nuclear retinoid X receptor agonists: A proteomic approach.

An attempt has been made to delineate the role of natural and synthetic retinoid receptor ligands on vimentin expression in the human triple-negative breast cancer cells. The effects of currently synthesized triorganotin derivatives of the general formula RSnX (R is butyl or phenyl, X is isothiocyanate), which are considered RXR ligands, were investigated in the human MDA-MB-231 breast cancer cell line. Studies were evaluated in the presence and absence of all-trans retinoic acid (ATRA), a natural RAR ligand.

Causal associations of autoimmune thyroiditis and papillary thyroid carcinoma: mRNA expression of selected nuclear receptors and other molecular targets.

Potential causal associations of autoimmune thyroiditis (AIT) and papillary thyroid carcinoma (PTC) have been studied previously. The mRNA expression patterns of thyroid hormone receptors (TR), retinoid receptors (RAR), rexinoid receptors (RXR), dihydroxyvitamin D receptors (VDR), and progesterone receptors (PR) in PTC tissue of patients without autoimmune thyroiditis (PTC/AIT-) and in PTC tissue of patients with coexisting AIT (PTC/AIT+) have been investigated in order to judge whether the observed changes may take part in the promotion and progression of thyroid cancer. Tumours with or without AIT were classified histologically and the semiquantitative PCR was performed.

Triorganotin Isothiocyanates Affect Migration and Immune Check-point Receptors in Human Triple-negative Breast Carcinoma MDA-MB-231 Cells.

Background/aim: Triple-negative breast cancer (TNBC) constitutes 15-20% of all breast carcinomas, affecting younger women more often and has a worse prognosis than other types of breast cancer, due to the combination of more aggressive clinical behavior and lack of molecular targets for therapy. This study assessed the effects of non-genotoxic concentrations of tributyltin isothiocyanate (TBT-ITC) and triphenyltin isothiocyanate (TPT-ITC) on MDA-MB-231 cells.

Materials And Methods: MTT assay, comet assay, kinetic imaging and flow cytometry were used for analysis of MDA-MB-231 cells.

Genotoxic Effects of Tributyltin and Triphenyltin Isothiocyanates, Cognate RXR Ligands: Comparison in Human Breast Carcinoma MCF 7 and MDA-MB-231 Cells.

The cytotoxicity of two recently synthesized triorganotin isothiocyanate derivatives, nuclear retinoid X receptor ligands, was tested and compared in estrogen-receptor-positive MCF 7 and -negative MDA-MB-231 human breast carcinoma cell lines. A 48 h MTT assay indicated that tributyltin isothiocyanate (TBT-ITC) is more cytotoxic than triphenyltin isothiocyanate (TPT-ITC) in MCF 7 cells, and the same trend was observed in the MDA-MB-231 cell line. A comet assay revealed the presence of both crosslinks and increasing DNA damage levels after the 17 h treatment with both derivatives.

Novel insights into the combined effect of triorganotin compounds and all-trans retinoic acid on expression of selected proteins associated with tumor progression in breast cancer cell line MDA-MB-231: Proteomic approach.

Trialkyltins and triaryltins function as nuclear retinoid X receptors (RXR) agonists due to their affinity to the ligand-binding domain of RXR subtypes and function as transcriptional activators. We present the data on combined effects of all-trans retinoic acid (ATRA), retinoic acid receptor (RAR) ligand and tributyltin chloride or triphenyltin chloride (RXR ligands) on protein pattern in MDA-MB-231 cells. Proteomic strategies based on bottom-up method were applied in this study.

Effects of selected triorganotin compounds on transcriptional activity of vitamin D3 receptor and peroxisome proliferator-activated receptor gamma.

Both, the vitamin D3 receptor (VDR) and the peroxisome proliferator-activated receptor gamma (PPARγ), are ligand-inducible transcription factors that control expressions of various genes involved in essential biological processes. Structurally diverse chemical substances are capable to bind to VDR and PPARγ, consequently acting in agonistic or antagonistic mode. Ubiquitous triorganotin compounds, key components of antifouling, disinfectant and biocidal agents were found to act as cognate ligands of several nuclear receptors.

Triorganotin Derivatives Induce Cell Death Effects on L1210 Leukemia Cells at Submicromolar Concentrations Independently of P-glycoprotein Expression.

The acceleration of drug efflux activity realized by plasma membrane transporters in neoplastic cells, particularly by P-glycoprotein (P-gp, ABCB1 member of the ABC transporter family), represents a frequently observed molecular cause of multidrug resistance (MDR). This multiple resistance represents a real obstacle in the effective chemotherapy of neoplastic diseases. Therefore, identifying cytotoxic substances that are also effective in P-gp overexpressing cells may be useful for the rational design of substances for the treatment of malignancies with developed MDR.

Stability studies of endocrine disrupting tributyltin and triphenyltin compounds in an artificial sea water model.

Triorganotins belong to toxic components present predominantly in antifouling paints for marine vessels. Tributyltin/triphenyltin at pico- or nanomolar concentrations in sea water are known to induce an irreversible sexual abnormality in females of over 190 marine species, an "imposex" phenomenon - the superimposition of male genitalia on a female. Moreover, trialkyltins and triaryltins function as potent nuclear retinoid X receptors (RXR) agonists.

Consequences of the natural retinoid/retinoid X receptor ligands action in human breast cancer MDA-MB-231 cell line: Focus on functional proteomics.

The main intention of this study was the investigation of impact of natural biologically active ligands of nuclear retinoid/retinoid X receptors (all-trans and 9-cis retinoic acid) on proteomic pattern in human estrogen receptor negative breast cancer cell line MDA-MB-231. For this purpose, proteomic strategies based on bottom-up method were applied. The total cell proteins were extracted utilizing a commercially Radio-Immunoprecipitation Assay (RIPA) buffer and separated on 2D sodium dodecyl sulfate polyacrylamide gel electrophoresis (2D SDS-PAGE).

Effects of natural ligands and synthetic triorganotin compounds of nuclear retinoid X receptors in human MCF-7 breast cancer cell line.

In the present study, we analyzed in vitro effects of natural and synthetic triorganotin ligands of nuclear retinoid X receptors in human MCF-7 breast cancer cells. Our data has shown that all-trans retinoic acid significantly reduced expression of RXRalpha mRNA, Bcl2 and enhanced expression of BAX proteins. Tributyltin bromide markedly decreased mRNA level of RXRalpha and RXRbeta.

Sn- and Ge- triorganometallics exert different cytotoxicity and modulation of migration in triple-negative breast cancer cell line MDA-MB-231.

Among a variety of metal containing organic compounds, tin derivatives are enjoying an increasing interest and appear to be very promising as potential drug candidates. We studied eight organometallic derivatives, nuclear retinoid X receptor (RXR) ligands and two germanium containing derivates that do not serve as RXR ligands. Tributylgermanium chloride (TBGe) and triphenylgermanium chloride (TPGe) did not inhibit growth of human triple negative MDA-MB-231 breast cancer cells.

The role of retinoic acid receptors and their cognate ligands in reproduction in a context of triorganotin based endocrine disrupting chemicals.

Retinoic acid (RA), an active form of vitamin A, regulates the embryonic development, male and female reproduction and induces important effects on the cell development, proliferation, and differentiation. These effects are mediated by the retinoid (RAR) and rexinoid nuclear receptors (RXR), which are considered to be a ligand-activated, DNA-binding, trans-acting, and transcription-modulating proteins, involved in a general molecular mechanism responsible for the transcriptional responses in target genes. Organotin compounds are typical environmental contaminants and suspected endocrine disrupting substances.

A comparative study of protein patterns of human estrogen receptor positive (MCF-7) and negative (MDA-MB-231) breast cancer cell lines.

In the present study, we analyzed the cell lysates of human tumour cell lines representing two major clinically different types of breast cancer. Our main goal was to show the differences between them on proteomic level. Gel electrophoresis followed by MALDI-TOF MS analysis was used for proteins determination.

Radioligand binding assay for accurate determination of nuclear retinoid X receptors: A case of triorganotin endocrine disrupting ligands.

Nuclear 9-cis retinoic acid receptors (retinoid X receptors, RXR) are promiscuous dimerization partners for a number of nuclear receptors. In the present study, we established a novel in vitro method for quantitative determination of the nuclear retinoid X receptors in rat liver. One type of high affinity and limited capacity RXR specific binding sites with the Ka value ranging from 1.

Anticancer effects of tributyltin chloride and triphenyltin chloride in human breast cancer cell lines MCF-7 and MDA-MB-231.

Triorganotin compounds induce hormonal alterations, i.e., endocrine-disrupting effects in mammals, including humans.

Relationship between histology, development and tumorigenesis of mammary gland in female rat.

The mammary gland is a dynamic organ that undergoes structural and functional changes associated with growth, reproduction, and post-menopausal regression. The postnatal transformations of the epithelium and stromal cells of the mammary gland may contribute to its susceptibility to carcinogenesis. The increased cancer incidence in mammary glands of humans and similarly of rodents in association with their development is believed to be partly explained by proliferative activity together with lesser degree of differentiation, but it is not completely understood how the virgin gland retains its higher susceptibility to carcinogenesis.