- Email: [email protected]
Anticancer effects of methanolic, supercritical CO2 rosemary extracts, carnosic acid and rosmarinic acid
New Biotechnology · Volume 29S · September 2012
mutated genes such as ARID1A and ARID2. Many of these genes display inactivating mutations indicating or suggesting a tumour suppressor function. Thus, although these genes may serve for diagnosis and prognosis purposes, they are not readily targetable for disease treatment. CTNNB1 is the only gene to be activated by mutation in HCC. It may serve as a target for drugs inhibiting Wnt–-catenin signalling. HCC cells display also epigenetic changes such as DNA methylation and hypomethylation, and histone modifications. Among others, EZH2, a histone methyltransferase is over-expressed in HCC cells and may affect histone-3 lysin-27 methylation status. Recently, we identified additional epigenetic regulators such as ATAD2 to be overexpressed in HCC. The talk will overview the current status of genetic and epigenetic aberrations in HCC. In addition, we will present our recent findings with regard to epigenetic factors involved in this disease. http://dx.doi.org/10.1016/j.nbt.2012.08.041 Oral 2.3.03 Anticancer effects of methanolic, supercritical CO2 rosemary extracts, carnosic acid and rosmarinic acid Canan Sevimli-Gur 1,2,∗ , Ozlem Yesil-Celiktas 1 , Fazilet VardarSukan 1 , Erdal Bedir 1 1
Department of Bioengineering, Faculty of Engineering, Ege University, 35100 Bornova, Izmir, Turkey 2 Department of Biology, Biotechnology Discipline, Science and Arts Faculty, 41380 Izmit, Kocaeli The leaves of Rosmarinus officinalis harvested from three different locations of Turkey were extracted by both methanolic and supercritical CO2 extraction. Subsequently, six extracts and the active compounds, carnosic acid, and rosmarinic acid were applied to various human cancer cell lines including NCI-H82 (human, small cell lung, carcinoma), DU-145 (human, prostate, carcinoma), Hep-3B (human, black, liver, carcinoma, hepatocellular), K-562 (human chronic myeloid leukemia), MCF-7 (human, breast, adenocarcinoma), PC-3 (human, prostate, adenocarcinoma) and MDA-MB-231 (human, breast, adenocarcinoma) by MTT assay. Supercritical CO2 extracts had superior antiproliferative effect compared to the soxhlet extracts. Although the extracts exhibited various cytotoxic effects against different cell lines, comparatively low IC50 values ranging between 12.50 and 47.55 g/ml were attained against K-562, being the most sensitive cell line. Moreover, carnosic acid caused the lowest cell viability with values ranging from 13 to 30% at a concentration of 19 M after 48 h of treatments, resulting in superior antiproliferative effect. Rosemary extract is a potential candidate to be included in the anti-cancer diet with pre-determined doses avoiding toxicity. Keywords: Rosmarinus officinalis; Carnosic acid; Rosmarinic acid; Anticarcinogen; Cytotoxicity; Supercritical CO2 extraction http://dx.doi.org/10.1016/j.nbt.2012.08.042
Stream: Red – Health & Medicine, Session: Personalised & Stratified Medicine Oral 2.4.01 The use of special populations to uncover the genetic background of common diseases Aarno Palotie 1,2,3 1
The Wellcome Trust Sanger Institute, Cambridge, UK FIMM, The Institute for Molecular Medicine Finland, Helsinki, Finland 3 The Broad Institute of Harvard and MIT, Cambridge, MA, United States 2
Delivery of healthcare in Europe is faced with the challenge of controlling ever-growing costs while satisfying an increased demand for quality. Developing means for more stratified, even personalized health care has been suggested as one strategy to address these challenges. However, in order to understand the factors underlying individual variability in biological makeup in the context of environmental differences, data need to be analysed in very large samples. GWA studies have identified thousands of gene loci associated to hundreds of traits and has improved our understanding of the genetic background of diseases common in the population. However, it is also evident that common variants identified in GWA studies explain only a fraction of the genetic variance underlying common traits. New sequencing techniques have enabled the identification of rare and low frequency variants in large samples. These variants are expected to contribute to the overall disease susceptibility. Finland is uniquely positioned to pioneer some of the challenges of delivery of personalised medicine because of well phenotyped population cohorts and centralized medical information systems. Finland has also a unique population history that enables disease gene discovery that would be difficult or even impossible in more heterogeneous or smaller isolated populations. The small founder population and multiple genetic bottlenecks have resulted in an enrichment of variants that are very rare in other European populations. This enrichment of low frequency variants is expected to provide opportunities to uncover cellular pathways that contribute to disease predispositions. These opportunities have stimulated large collaborative sequencing initiatives of Finnish cohorts called the SISu Project (Sequencing Initiative Suomi (Suomi is the Finnish name for Finland)). The SISu project brings together the strongest genomic research resources worldwide, some of the largest epidemiological study collections and advanced health care data analysis informatics by joining forces across Europe and USA. The aim of the project is to provide both new insight in the pathogenetic mechanisms of common disease traits and to develop genome health tools for personalized medicine of these diseases. The long term aim is to develop new analysis tools to integrate genomic data and phenotype data; and finally to evaluate the generalizability of these findings in the more general European genetic landscape. Design of a novel antimicrobial peptide activated by virulent proteases. http://dx.doi.org/10.1016/j.nbt.2012.08.043
S18
www.elsevier.com/locate/nbt
mutated genes such as ARID1A and ARID2. Many of these genes display inactivating mutations indicating or suggesting a tumour suppressor function. Thus, although these genes may serve for diagnosis and prognosis purposes, they are not readily targetable for disease treatment. CTNNB1 is the only gene to be activated by mutation in HCC. It may serve as a target for drugs inhibiting Wnt–-catenin signalling. HCC cells display also epigenetic changes such as DNA methylation and hypomethylation, and histone modifications. Among others, EZH2, a histone methyltransferase is over-expressed in HCC cells and may affect histone-3 lysin-27 methylation status. Recently, we identified additional epigenetic regulators such as ATAD2 to be overexpressed in HCC. The talk will overview the current status of genetic and epigenetic aberrations in HCC. In addition, we will present our recent findings with regard to epigenetic factors involved in this disease. http://dx.doi.org/10.1016/j.nbt.2012.08.041 Oral 2.3.03 Anticancer effects of methanolic, supercritical CO2 rosemary extracts, carnosic acid and rosmarinic acid Canan Sevimli-Gur 1,2,∗ , Ozlem Yesil-Celiktas 1 , Fazilet VardarSukan 1 , Erdal Bedir 1 1
Department of Bioengineering, Faculty of Engineering, Ege University, 35100 Bornova, Izmir, Turkey 2 Department of Biology, Biotechnology Discipline, Science and Arts Faculty, 41380 Izmit, Kocaeli The leaves of Rosmarinus officinalis harvested from three different locations of Turkey were extracted by both methanolic and supercritical CO2 extraction. Subsequently, six extracts and the active compounds, carnosic acid, and rosmarinic acid were applied to various human cancer cell lines including NCI-H82 (human, small cell lung, carcinoma), DU-145 (human, prostate, carcinoma), Hep-3B (human, black, liver, carcinoma, hepatocellular), K-562 (human chronic myeloid leukemia), MCF-7 (human, breast, adenocarcinoma), PC-3 (human, prostate, adenocarcinoma) and MDA-MB-231 (human, breast, adenocarcinoma) by MTT assay. Supercritical CO2 extracts had superior antiproliferative effect compared to the soxhlet extracts. Although the extracts exhibited various cytotoxic effects against different cell lines, comparatively low IC50 values ranging between 12.50 and 47.55 g/ml were attained against K-562, being the most sensitive cell line. Moreover, carnosic acid caused the lowest cell viability with values ranging from 13 to 30% at a concentration of 19 M after 48 h of treatments, resulting in superior antiproliferative effect. Rosemary extract is a potential candidate to be included in the anti-cancer diet with pre-determined doses avoiding toxicity. Keywords: Rosmarinus officinalis; Carnosic acid; Rosmarinic acid; Anticarcinogen; Cytotoxicity; Supercritical CO2 extraction http://dx.doi.org/10.1016/j.nbt.2012.08.042
Stream: Red – Health & Medicine, Session: Personalised & Stratified Medicine Oral 2.4.01 The use of special populations to uncover the genetic background of common diseases Aarno Palotie 1,2,3 1
The Wellcome Trust Sanger Institute, Cambridge, UK FIMM, The Institute for Molecular Medicine Finland, Helsinki, Finland 3 The Broad Institute of Harvard and MIT, Cambridge, MA, United States 2
Delivery of healthcare in Europe is faced with the challenge of controlling ever-growing costs while satisfying an increased demand for quality. Developing means for more stratified, even personalized health care has been suggested as one strategy to address these challenges. However, in order to understand the factors underlying individual variability in biological makeup in the context of environmental differences, data need to be analysed in very large samples. GWA studies have identified thousands of gene loci associated to hundreds of traits and has improved our understanding of the genetic background of diseases common in the population. However, it is also evident that common variants identified in GWA studies explain only a fraction of the genetic variance underlying common traits. New sequencing techniques have enabled the identification of rare and low frequency variants in large samples. These variants are expected to contribute to the overall disease susceptibility. Finland is uniquely positioned to pioneer some of the challenges of delivery of personalised medicine because of well phenotyped population cohorts and centralized medical information systems. Finland has also a unique population history that enables disease gene discovery that would be difficult or even impossible in more heterogeneous or smaller isolated populations. The small founder population and multiple genetic bottlenecks have resulted in an enrichment of variants that are very rare in other European populations. This enrichment of low frequency variants is expected to provide opportunities to uncover cellular pathways that contribute to disease predispositions. These opportunities have stimulated large collaborative sequencing initiatives of Finnish cohorts called the SISu Project (Sequencing Initiative Suomi (Suomi is the Finnish name for Finland)). The SISu project brings together the strongest genomic research resources worldwide, some of the largest epidemiological study collections and advanced health care data analysis informatics by joining forces across Europe and USA. The aim of the project is to provide both new insight in the pathogenetic mechanisms of common disease traits and to develop genome health tools for personalized medicine of these diseases. The long term aim is to develop new analysis tools to integrate genomic data and phenotype data; and finally to evaluate the generalizability of these findings in the more general European genetic landscape. Design of a novel antimicrobial peptide activated by virulent proteases. http://dx.doi.org/10.1016/j.nbt.2012.08.043
S18
www.elsevier.com/locate/nbt