BIRC5 (baculoviral IAP repeat containing 5)

BIRC5, also known as survivin, has been implicated in cell cycle progression and apoptosis avoidance. BIRC5 is highly expressed in embryonic tissues, however very low or absent in adult tissues. BIRC5 overexpression has been frequently associated to cancer development, a poor prognosis and chemoresistance. Besides that, different BIRC5 isoforms has been characterized and related to better or worse chemotherapy responses depending on the isoform and the cancer type. So far, many efforts have been conducted in order to deplete BIRC5 in cancer cells, including gene therapy, pharmacological and nanotechnological approaches. In this review, we will discuss the role of BIRC5 in cancer cell biology and its clinical significance, demonstrating its DNA/RNA and protein aspects, also its relevance for diagnosis and prognosis, and advances as a target for the treatment of different cancer types

XIAP (X-linked inhibitor of apoptosis)

X-linked inhibitor of apoptosis (XIAP), also referred to as BIRC4 or IAP3, is one of the most studied members among the proteins known as Inhibitors of Apoptosis Proteins (IAPs). This protein family portrays its main role by preventing apoptotic cell death through direct or indirect inhibition of caspase activity. All members of the IAPs carry at least one BIR domain in their structure, which are generally responsible for caspase interaction. XIAP has three BIR domains, enabling interaction with both initiation and effector caspases. Moreover, it is also structured with a RING finger domain, which functions as a ubiquitin ligase (E3), and one UBA domain, for binding to ubiquitin, further rendering XIAP a central role in the ubiquitination process and, thus, implicating such IAP in multiple signaling pathways, including cell death, autophagy, immunity, inflammation, cell cycle, and cell migration. XIAP overexpression is found in a variety of cancer types and is frequently associated with chemoresistance and increased risk of relapse. Furthermore, there are many evidences that XIAP inhibition may sensitize tumor cells to chemotherapy agents, which make this protein a potential target in cancer

Cytotoxic lipidic α-amino acids from the zoanthid Protopalythoa variabilis from the Northeastern coast of Brazil

Two lipidic α-amino acids 1a and 1b were isolated from the zoanthid Protopalythoa variabilis using a bioguided fractionation for cytotoxic activity. The structures of the metabolites were determined by spectroscopic methods, including NMR (nuclear magnetic resonance) ¹H e 13C, IR (infrared) and high resolution mass spectrometry (positive mode). The cytotoxic activity of the crude extract, as well as of the mixture of 1a and 1b were measured in vitro using the MTT assay for four human tumor cell lines. This finding has important biological and chemical implications for this type of compound. This is the first report of lipidic α-amino acids from natural sources, as well as of their cytotoxic activity.Dois α-aminoácidos lipídicos 1a e 1b foram isolados do zoantídeo Protopalythoa variabilis através de fracionamento guiado pela atividade citotóxica. As estruturas foram determinadas por diferentes métodos espectroscópicos, tais como, RMN (ressonância magnética nuclear) ¹H e 13C, IV (infravermelho) e espectrometria de massa de alta resolução (modo positivo). A atividade citotóxica dos extratos, das frações e 1a/1b foi avaliada in vitro através do teste do MTT contra quatro linhagens de células tumorais. Este achado tem implicações biológicas e químicas importantes para essa classe de compostos. Este é o primeiro relato de α-aminoácidos lipídicos a partir de uma fonte natural, bem como de sua atividade citotóxica.CNPqFINEPInstitute Claude Bernar

In vitro metabolism studies of erythraline, the major spiroalkaloid from Erythrina verna

Abstract\ud \ud Background\ud \ud Erythrina verna, popularly known as “mulungu”, is a Brazilian medicinal plant used to treat anxiety. Erythrina alkaloids have been described in several species of Erythrina, which have biological and therapeutic properties well known that include anxiolytic and sedative effects.\ud \ud \ud Methods\ud In this work, in vitro metabolism of erythraline (1), the major spirocyclic alkaloid of Erythrina verna, was studied in the pig cecum model and by biomimetic phase I reactions. The biomimetic reactions were performed with Jacobsen catalyst to produce oxidative metabolites and one metabolite was isolated and evaluated against cancer cells, as HL-60 (promyelocytic leukemia), SF-295 (Glioblastoma) and OVCAR-8 (ovarian carcinoma).\ud \ud \ud Results\ud Erythraline exhibited no metabolization by the pig microbiota and a main putative metabolite was formed in a biomimetic model using Jacobsen catalyst. This metabolite was isolated and identified as 8-oxo-erythraline (2). Finally, erythraline and the putative metabolite were tested in MTT model and both compounds showed no important cytotoxic activity against tumor cells.\ud \ud \ud Conclusions\ud The alkaloid erythraline was not metabolized by intestinal microbiota, but it was possible to identify its oxidative metabolite from biomimetic reactions. So these data are interesting and stimulate other studies involving this alkaloid, since it is present in phytomedicine products and there are not reported data about the metabolism of erythrina alkaloids.The authors gratefully acknowledge FAPESP (Process: 2010/07413-0, 2011/\ud 13281-2, 2012/18031-7), CAPES, CNPq (201691/2011-6) and INCT-if for financial\ud support. The authors also thanks Kurzen family (farmers) for the ceca supplying

In vivo antitumoural activity and composition of an oil extract of Brazilian propolis

AbstractThe present study aimed to evaluate in vivo and in vitro the antitumoural activity of a propolis extract obtained with edible vegetable oil and its fractions and also to investigate its chemical composition by LC–MS and LC–MS/MS. To evaluate the toxicological aspects related to the propolis extract treatment, hematological, biochemical, histopathological and morphological analyses of treated animals were performed. All propolis extracts showed an in vivo antitumour activity in the experimental model with a moderate toxicity effect at experimental exposure levels. The oil extract was as effective as the ethanolic extract at inhibiting tumour growth. In vitro assays showed that the whole oil extract produced better inhibition of tumour cells than its fractions. LC–MS and LC–MS/MS identified four phenolic acids and three flavonoids. The anticancer potential of the oil extract of propolis has been demonstrated and the edible vegetable oil was shown as an attractive alternative solvent to extract bioactive natural propolis components

Constituintes químicos da ascídia didemnum psammatodes (sluiter, 1895) coletada na costa cearense Chemical constituent from the ascidian didemnum psammatodes (sluiter, 1895) collecter on the shores of ceara state

<abstract language="eng">Chemical investigation of the methanolic extract of the ascidian Didemnum psammatodes has led to the identification of the nucleosides 2'-deoxyuridine (1), thymidine (2), 2'-deoxyinosine (3) and 2'-deoxyguanosine (4), the steroids cholestanol, cholestanone and stigmasterol in mixture and batyl alcohol plus two analogs, 1-heptadecyloxy-2,3-propanediol and 1-nonadecyloxy-2,3-propanediol in mixture. Their structures were proposed by NMR, MS and comparison with literature data and GC-MS analysis

Pyrimidine alkaloids from Eudistoma vannamei

Abstract Methanolic extracts of the Brazilian endemic ascidian Eudistoma vannamei have been extensively studied for their cytotoxic activity against several human cancer cell lines. Previous work reported the occurrence of purine derivatives and staurosporine alkaloids as the major nitrogen-containing compounds. In this study, we report the occurrence of three pyrimidine alkaloids in addition to cholesterol, sitosterol and stigmasterol