Citrus peel flavonoids as potential cancer prevention agents

Citrus fruit and in particular flavonoid compounds from citrus peel have been identified as agents with utility in the treatment of cancer. This review provides a background and overview regarding the compounds found within citrus peel with putative anticancer potential as well as the associated in vitro and in vivo studies. Historical studies have identified a number of cellular processes that can be modulated by citrus peel flavonoids including cell proliferation, cell cycle regulation, apoptosis, metastasis, and angiogenesis. More recently, molecular studies have started to elucidate the underlying cell signaling pathways that are responsible for the flavonoids' mechanism of action. These growing data support further research into the chemopreventative potential of citrus peel extracts, and purified flavonoids in particular. This critical review highlights new research in the field and synthesizes the pathways modulated by flavonoids and other polyphenolic compounds into a generalized schema

Dietary Manipulation for Therapeutic Effect in Prostate Cancer

Given that there is a wealth of literature on the potential effect of a wide variety of phytochemicals on the growth of prostate cancer cells, we have limited our discussion to arguably four of the most important: isoflavones, lycopene, resveratrol, and curcumin. The focus of this review is on the clinical pharmacology of these compounds, as there are already an extensive number of reviews in the literature on all of these compounds for various cancers, including our previous review of isoflavones in prostate cancer (de Souza et al., 2009). Here, we use the loose term “phytochemicals” to describe this group of plant–based compounds with biological activity in vitro, for simplicity. Like other phytochemicals, isoflavones, lycopene, resveratrol and curcumin have a wide variety of potential mechanisms of action in many different cancer cell lines. Many of these biological effects involve key components of signal transduction pathways within cancer cells, but in this review, we will be focusing on studies specifically in prostate cancer

Egress of HSV-1 capsid requires the interaction of VP26 and a cellular tetraspanin membrane protein

HSV-1 viral capsid maturation and egress from the nucleus constitutes a self-controlled process of interactions between host cytoplasmic membrane proteins and viral capsid proteins. In this study, a member of the tetraspanin superfamily, CTMP-7, was shown to physically interact with HSV-1 protein VP26, and the VP26-CTMP-7 complex was detected both in vivo and in vitro. The interaction of VP26 with CTMP-7 plays an essential role in normal HSV-1 replication. Additionally, analysis of a recombinant virus HSV-1-UG showed that mutating VP26 resulted in a decreased viral replication rate and in aggregation of viral mutant capsids in the nucleus. Together, our data support the notion that biological events mediated by a VP26 - CTMP-7 interaction aid in viral capsid enveloping and egress from the cell during the HSV-1 infectious process

Towards a framework for better understanding of quiescent cancer cells

Quiescent cancer cells (QCCs) are cancer cells that are reversibly suspended in G0 phase with the ability to re-enter the cell cycle and initiate tumor growth, and, ultimately, cancer recurrence and metastasis. QCCs are also therapeutically challenging due to their resistance to most conventional cancer treatments that selectively act on proliferating cells. Considering the significant impact of QCCs on cancer progression and treatment, better understanding of appropriate experimental models, and the evaluation of QCCs are key questions in the field that have direct influence on potential pharmacological interventions. Here, this review focuses on existing and emerging preclinical models and detection methods for QCCs and discusses their respective features and scope for application. By providing a framework for selecting appropriate experimental models and investigative methods, the identification of the key players that regulate the survival and activation of QCCs and the development of more effective QCC-targeting therapeutic agents may mitigate the consequences of QCCs

Neonatal rhesus monkey is a potential animal model for studying pathogenesis of EV71 infection

AbstractData from limited autopsies of human patients demonstrate that pathological changes in EV71-infected fatal cases are principally characterized by clear inflammatory lesions in different parts of the CNS; nearly identical changes were found in murine, cynomolgus and rhesus monkey studies which provide evidence of using animal models to investigate the mechanisms of EV71 pathogenesis. Our work uses neonatal rhesus monkeys to investigate a possible model of EV71 pathogenesis and concludes that this model could be applied to provide objective indicators which include clinical manifestations, virus dynamic distribution and pathological changes for observation and evaluation in interpreting the complete process of EV71 infection. This induced systemic infection and other collected indicators in neonatal monkeys could be repeated; the transmission appears to involve infecting new monkeys by contact with feces of infected animals. All data presented suggest that the neonatal rhesus monkey model could shed light on EV71 infection process and pathogenesis

Human Group IIA Phospholipase A2 : three decades on from its discovery

Phospholipase A2 (PLA2) enzymes were first recognized as an enzyme activity class in 1961. The secreted (sPLA2) enzymes were the first of the five major classes of human PLA2s to be identified and now number nine catalytically-active structurally homologous proteins. The best-studied of these, group IIA sPLA2, has a clear role in the physiological response to infection and minor injury and acts as an amplifier of pathological inflammation. The enzyme has been a target for anti-inflammatory drug development in multiple disorders where chronic inflammation is a driver of pathology since its cloning in 1989. Despite intensive effort, no clinically approved medicines targeting the enzyme activity have yet been developed. This review catalogues the major discoveries in the human group IIA sPLA2 field, focusing on features of enzyme function that may explain this lack of success and discusses future research that may assist in realizing the potential benefit of targeting this enzyme. Functionally-selective inhibitors together with isoform-selective inhibitors are necessary to limit the apparent toxicity of previous drugs. There is also a need to define the relevance of the catalytic function of hGIIA to human inflammatory pathology relative to its recently-discovered catalysis-independent function

Phospholipase

Phospholipase A2 (PLA2) enzymes are a family of proteins and to date at least 20 members have been identified in mammals. The family can be classified into four classes on the basis of their nucleotide and amino acid sequence homology. First, there are at present ten secreted phospholipase A2 enzymes (sPLA2-IB, -IIA, -IIC, -IID, -IIE, -IIF, -III, -V, -X, and -XII), which are of low molecular weight (13–18 kDa) with a catalytic histidine in their active site and a requirement for calcium for enzyme activity. Second, there are three characterized human cytosolic PLA2 enzymes (cPLA2-α, -β, and -γ, also known as Group IVA, IVB, and IVC PLA2) that use a catalytic serine in their active site. cPLA2-α and -β contain a C2 calcium binding domain and enzyme activity is calcium-dependent while cPLA2-γ lacks this domain and is thus a calcium-independent PLA2. Recently, a comprehensive homology search against the murine genome and EST databases using conserved sequences of cPLA2 as the query, led to the identification of cPLA2-δ, cPLA2-ε, and cPLA2-ξ (also known as Group IVD, IVE, and IVF PLA2), all of which are calcium-dependent enzymes. Third, three calcium-independent cytosolic PLA2 enzymes (iPLA2-α, -β, and -γ also known as Group VIA-1, VIA-2, and VIB) with an active-site serine, and fourth, four platelet-activating factor acetylhydrolase (PAF-AH) enzymes (Group VIIA, VIIB, VIIIA, and VIIIB) also involve a catalytic serine. Many of the different forms of PLA2 are differentially expressed in a tissue-, species-, and/or genotype-specific manner