142 research outputs found
2,3,7,8-tetrachlorodibenzo-p-dioxin and the viral infection
Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), a widespread highly toxic environmental contaminant, suppresses immune response and leads to an increased susceptibility to infectious agents. In particular, several studies have provided evidence that TCDD decreases resistance to numerous viruses. Indeed, in vivo and in vitro investigations showed that the presence of TCDD is able to interfere with the replication of both human and animal viruses, such as influenza A viruses, coxsackie virus B3, immunodeficiency virus type-1 (HIV-1), cytomegalovirus (CMV), herpes simplex II, and bovine herpesvirus 1. Moreover, TCDD could induce an exacerbation of latent infection produced by HIV-1, CMV or Epstein-Barr virus. In this review, we first describe the general effects of TCDD exposure on mammalian cells, then we focus on its influence on the viral infections. Overall, the available data support the concept that TCDD exposure may act as an additional risk factor in promoting of viral diseases
Ultraviolet B and A irradiation induces fibromodulin expression in human fibroblasts in vitro
Ultraviolet (UV) radiation affects the extracellular matrix (ECM) of the human skin. The small leucine-rich repeat protein fibromodulin interacts with type I and II collagen fibrils, thereby affecting ECM assembly. The aim of this study was to evaluate whether short wave UV (UVB) or long wave UV (UVA) irradiation influences fibromodulin expression. Exponentially growing human fibroblasts (IMR-90 cells) were exposed to increasing doses of UVB (2.5-60 mJ/cm(2)) or UVA (0.5-10 J/cm(2)). After UV irradiation fibromodulin, p21 and GADD45 levels were evaluated as well as cell viability, reactive oxygen species formation (ROS) and DNA damage. We found that fibromodulin expression: (i) increased after UVB and UVA irradiation; (ii) was 10-fold higher after UVA (10 J/cm(2)) versus 5-fold with UVB (10 mJ/cm(2)); (iii) correlated with reactive oxygen species formation, particularly after UVA; and (iv) was linked to the DNA damage binding protein (DDB1) translocation in the nucleus, particularly after UVB. These results further suggest that the UV-induced fibromodulin increase could counteract the UV-induced connective tissue damage, promoting the assembly of new collagen fibrils
Bioactivity and Development of Small Non-Platinum Metal-Based Chemotherapeutics
Countless expectations converge in the multidisciplinary endeavour for the search and
development of effective and safe drugs in fighting cancer. Although they still embody a minority of the pharmacological agents currently in clinical use, metal-based complexes have great yet unexplored potential, which probably hides forthcoming anticancer drugs. Following the historical success of cisplatin and congeners, but also taking advantage of conventional chemotherapy limitations that emerged with applications in the clinic, the design and development of non-platinum metal-based chemotherapeutics, either as drugs or prodrugs, represents a rapidly evolving field wherein candidate compounds can be fine-tuned to access interactions with druggable biological targets. Moving in this direction, over the last few decades platinum family metals, e.g., ruthenium and palladium, have been largely proposed. Indeed, transition metals and molecular platforms where they originate are endowed with unique chemical and biological features based on, but not limited to, redox activity and coordination geometries, as well as ligand selection (including their inherent reactivity
and bioactivity). Herein, current applications and progress in metal-based chemoth are reviewed.
Converging on the recent literature, new attractive chemotherapeutics based on transition metals other than platinumâand their bioactivity and mechanisms of actionâare examined and discussed.
A special focus is committed to anticancer agents based on ruthenium, palladium, rhodium, and
iridium, but also to gold derivatives, for which more experimental data are nowadays available. Next to platinum-based agents, ruthenium-based candidate drugs were the first to reach the stage of clinical evaluation in humans, opening new scenarios for the development of alternative chemotherapeutic options to treat cancer
Guanine-based amphiphiles: synthesis, ion transport properties and biological activity
Novel amphiphilic guanine derivatives, here named Gua1 and Gua2, have been prepared through few, simple and efficient synthetic steps. In ion transport experiments through phospholipid bilayers, carried out to evaluate their ability to mediate H(+) transport, Gua2 showed high activity. When this compound was investigated for ion-selective transport activities, no major differences were observed in the behaviour with cations while, in the case of anions, selective activity was observed in the series I(-)>Br(-)>Cl(-)>F(-). The bioactivity of these guanine analogues has been evaluated on a panel of human tumour and non-tumour cell lines in preliminary in vitro cytotoxicity assays, showing a relevant antiproliferative profile for Gua2
Anticancer Ruthenium(III) Complexes and Ru(III)-Containing Nanoformulations: An Update on the Mechanism of Action and Biological Activity
The great advances in the studies on metal complexes for the treatment of different cancer
forms, starting from the pioneering works on platinum derivatives, have fostered an increasingly
growing interest in their properties and biomedical applications. Among the various metal-containing
drugs investigated thus far, ruthenium(III) complexes have emerged for their selective cytotoxic
activity in vitro and promising anticancer properties in vivo, also leading to a few candidates in
advanced clinical trials. Aiming at addressing the solubility, stability and cellular uptake issues of low
molecular weight Ru(III)-based compounds, some research groups have proposed the development
of suitable drug delivery systems (e.g., taking advantage of nanoparticles, liposomes, etc.) able to
enhance their activity compared to the naked drugs. This review highlights the unique role of Ru(III)
complexes in the current panorama of anticancer agents, with particular emphasis on Ru-containing
nanoformulations based on the incorporation of the Ru(III) complexes into suitable nanocarriers in
order to enhance their bioavailability and pharmacokinetic properties. Preclinical evaluation of these
nanoaggregates is discussed with a special focus on the investigation of their mechanism of action at
a molecular level, highlighting their pharmacological potential in tumour disease models and value
for biomedical applications
Promelanogenic Effects by an Annurca Apple-Based Natural Formulation in Human Primary Melanocytes
Introduction
Melanocytes are engaged in synthesis, transport, and release of pigments at the epidermal-melanin units in response to the finely regulated melanogenic pathway. A multifaceted combination of both intrinsic and extrinsic factors â from endocrine and paracrine dynamics to exogenous stimuli such as sunlight and xenobiotics â modulates expression and activity of proteins involved in pigmentation, including the rate-limiting enzyme tyrosinase. As well as playing critical physiological functions comprising skin photoprotection, melanins define hair and skin pigmentation which in turn have impacted considerably to human social communication since time immemorial. Additionally, numerous skin diseases based on pigmentation alterations can have serious public influence. While several melanogenesis inhibitors are already available, the number of melanin activators and tyrosinase stimulators as drug-like agents is still limited.
Methods
To explore the biological effects of an Annurca Apple-based nutraceutical preparation (AMS) on melanin production, experiments in cellular models of human skin were performed. Both primary cultures and co-cultures of epidermal melanocytes (HEMa) and follicular keratinocytes (HHFK) were used.
Results
We show that AMS, by now branded for its cutaneous beneficial effects, induces in total biocompatibility a significant promelanogenic effect in human primary melanocytes. In line, we found melanin cytosolic accumulation consistent with tyrosinase up-regulation.
Conclusion
Disposal of skin pigmenting agents would be attractive for the treatment of hypopigmentation disorders, to postpone skin photoaging or simply for fashion, so that discovery and development of melanogenesis stimulators, especially from natural sources, is nowadays a dynamic area of research
Regulatory role of rpL3 in cell response to nucleolar stress induced by Act D in tumor cells lacking functional p53
Many chemotherapeutic drugs cause nucleolar stress and p53-independent pathways mediating the nucleolar stress response are emerging. Here, we demonstrate that ribosomal stress induced by Actinomycin D (Act D) is associated to the up-regulation of ribosomal protein L3 (rpL3) and its accumulation as ribosome-free form in lung and colon cancer cell lines devoid of p53. Free rpL3 regulates p21 expression at transcriptional and post-translational levels through a molecular mechanism involving extracellular-signal-regulated kinases1/2 (ERK1/2) and mouse double minute-2 homolog (MDM2). Our data reveal that rpL3 participates to cell response acting as a critical regulator of apoptosis and cell migration. It is noteworthy that silencing of rpL3 abolishes the cytotoxic effects of Act D suggesting that the loss of rpL3 makes chemotherapy drugs ineffective while rpL3 overexpression was associated to a strong increase of Act D-mediated inhibition of cell migration. Taking together our results show that the efficacy of Act D chemotherapy depends on rpL3 status revealing new specific targets involved in the molecular pathways activated by Act D in cancers lacking of p53. Hence, the development of treatments aimed at upregulating rpL3 may be beneficial for the treatment of these cancers
perspectives and potential applications of ruthenium based nanocarriers for cancer therapy
Perspectives and Potential Applications of Ruthenium-Based Nanocarriers for Cancer Therapy Rita Santamaria*1 , Carlo Irace1, Gerardino D'Errico 2, Daniela Montesarchio2 and Luigi Paduano2 1Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, I-80131, Napoli, Italy 2Department of Chemical Sciences, University of Napoli "Federico II", Complesso Universitario di Monte Sant'Angelo, via Cintia 21, I-80126, Napoli, Italy *Corresponding author: Rita Santamaria, Associate Professor, Department of Pharmacy, University of Napoli "Federico II", via D. Montesano 49, I-80131, Napoli, Italy, Fax: 0039081678403, Tel: 0039 081678421, E-Mail: [email protected] Citation: Rita Santamaria, Carlo Irace, Gerardino D'Errico, Daniela Montesarchio, Luigi Paduano (2013) Perspectives and Potential Applications of Ruthenium-Based Nanocarriers for Cancer Therapy. J Pharm Drug Devel 1(2): e201. doi: 10.15744/2348-9782.1.e201 Received Date: September 30, 2013 Accepted Date: October 15, 2013 Published Date: October 23, 2013 Editorial Open Acces
Cysteine Prevents the Reduction in Keratin Synthesis Induced by Iron Deficiency in Human Keratinocytes
L-cysteine is currently recognized as a conditionally essential sulphur amino acid. Besides contributing to many biological pathways, cysteine is a key component of the keratin protein by its ability to form disulfide bridges that confer strength and rigidity to the protein. In addition to cysteine, iron represents another critical factor in regulating keratins expression in epidermal tissues, as well as in hair follicle growth and maturation. By focusing on human keratinocytes, the aim of this study was to evaluate the effect of cysteine supplementation as nutraceutical on keratin biosynthesis, as well as to get an insight on the interplay of cysteine availability and cellular iron status in regulating keratins expression in vitro. Herein we demonstrate that cysteine promotes a significant up-regulation of keratins expression as a result of de novo protein synthesis, while the lack of iron impairs keratin expression. Interestingly, cysteine supplementation counteracts the adverse effect of iron deficiency on cellular keratin expression. This effect was likely mediated by the up-regulation of transferrin receptor and ferritin, the main cellular proteins involved in iron homeostasis, at last affecting the labile iron pool. In this manner, cysteine may also enhance the metabolic iron availability for DNA synthesis without creating a detrimental condition of iron overload. To the best of our knowledge, this is one of the first study in an in vitro keratinocyte model providing evidence that cysteine and iron cooperate for keratins expression, indicative of their central role in maintaining healthy epithelia. This article is protected by copyright. All rights reserved
Breast cancer chemotherapeutic options: a general overview on the preclinical validation of a multi-target ruthenium(III) complex lodged in nucleolipid nanosystems
In this review we have showcased the preclinical development of original amphiphilic
nanomaterials designed for rutheniumâbased anticancer treatments, to be placed within the current
metallodrugs approach leading over the past decade to advanced multitarget agents endowed with
limited toxicity and resistance. This strategy could allow for new options for breast cancer (BC)
interventions, including the tripleânegative subtype (TNBC) with poor therapeutic alternatives. BC
is currently the second most widespread cancer and the primary cause of cancer death in women.
Hence, the availability of novel chemotherapeutic weapons is a basic requirement to fight BC
subtypes. Anticancer drugs based on ruthenium are among the most explored and advanced nextgeneration
metallotherapeutics, with NAMIâA and KP1019 as two iconic ruthenium complexes
having undergone clinical trials. In addition, many nanomaterial Ru complexes have been recently
conceived and developed into anticancer drugs demonstrating attractive properties. In this field,
we focused on the evaluation of a Ru(III) complexânamed AziRuâincorporated into a suite of both
zwitterionic and cationic nucleolipid nanosystems, which proved to be very effective for the in vivo
targeting of breast cancer cells (BBC). Mechanisms of action have been widely explored in the
context of preclinical evaluations in vitro, highlighting a multitarget action on cell death pathways
which are typically deregulated in neoplasms onset and progression. Moreover, being AziRu
inspired by the wellâknown NAMIâA complex, information on nonânanostructured Ruâbased
anticancer agents have been included in a precise manner
- âŠ