Yu Hu1, Chun-yan Sun, Jing Huang, Liu Hong, Lu Zhang, Zhang-bo Chu. 1. Institute of Haematology, Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, China. ayan0618@163.com
Abstract
BACKGROUND: In multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells. METHODS: RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25 - 50.00 micromol/L) for different times (12 - 72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA). RESULTS: Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression. CONCLUSIONS: Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.
BACKGROUND: In multiple myeloma (MM), bone marrow angiogenesis parallels tumour progression and correlates with disease activity. Recent studies have proved resveratrol possesses antiangiogenic activity in vitro and in vivo. In this study, we examined the effects of resveratrol on myeloma cell dependent angiogenesis and the effects of resveratrol on some important angiogenic factors of RPMI 8226 cells. METHODS:RPMI 8226 cells were cocultured with human umbilical vein endothelial cells (HUVECs) to evaluate the effects of myeloma cells on angiogenesis. The RPMI 8226 cells were treated with various concentrations of resveratrol (6.25 - 50.00 micromol/L) for different times (12 - 72 hours). Reverse transcriptase polymerase chain reaction (RT-PCR) was used to assay vascular endothelial growth factor (VEGF), basic fibroblast growth factor (bFGF), metalloproteinases (MMP)-2 and MMP-9 mRNA. Gelatin zymography was used to analyze MMP-2 and MMP-9 activity. VEGF and bFGF proteins secreted by the cells in the medium were quantified by enzyme linked immunosorbent assay (ELISA). RESULTS: Cell proliferation, migration and differentiation of HUVECs markedly increased by coculture with RPMI 8226 cells. Resveratrol inhibited proliferation, migration and tube formation of HUVECs cocultured with myeloma cells in a dose dependent manner. Treatment of RPMI 8226 cells with resveratrol caused a decrease in MMP-2 and MMP-9 activity. Resveratrol inhibited VEGF and bFGF protein expression in a dose and time dependent manner. Furthermore, decreased levels of VEGF, bFGF, MMP-2 and MMP-9 mRNA from cells treated with various concentrations of resveratrol confirmed its antiangiogenic action at the level of gene expression. CONCLUSIONS:Resveratrol inhibits multiple myeloma angiogenesis by regulating expression and secretion of VEGF, bFGF, MMP-2 and MMP-9. Resveratrol may be a potential candidate for the treatment of multiple myeloma.
Authors: Mark A Feitelson; Alla Arzumanyan; Rob J Kulathinal; Stacy W Blain; Randall F Holcombe; Jamal Mahajna; Maria Marino; Maria L Martinez-Chantar; Roman Nawroth; Isidro Sanchez-Garcia; Dipali Sharma; Neeraj K Saxena; Neetu Singh; Panagiotis J Vlachostergios; Shanchun Guo; Kanya Honoki; Hiromasa Fujii; Alexandros G Georgakilas; Alan Bilsland; Amedeo Amedei; Elena Niccolai; Amr Amin; S Salman Ashraf; Chandra S Boosani; Gunjan Guha; Maria Rosa Ciriolo; Katia Aquilano; Sophie Chen; Sulma I Mohammed; Asfar S Azmi; Dipita Bhakta; Dorota Halicka; W Nicol Keith; Somaira Nowsheen Journal: Semin Cancer Biol Date: 2015-04-17 Impact factor: 15.707
Authors: Zari Dastani; Marie-France Hivert; Nicholas Timpson; John R B Perry; Xin Yuan; Robert A Scott; Peter Henneman; Iris M Heid; Jorge R Kizer; Leo-Pekka Lyytikäinen; Christian Fuchsberger; Toshiko Tanaka; Andrew P Morris; Kerrin Small; Aaron Isaacs; Marian Beekman; Stefan Coassin; Kurt Lohman; Lu Qi; Stavroula Kanoni; James S Pankow; Hae-Won Uh; Ying Wu; Aurelian Bidulescu; Laura J Rasmussen-Torvik; Celia M T Greenwood; Martin Ladouceur; Jonna Grimsby; Alisa K Manning; Ching-Ti Liu; Jaspal Kooner; Vincent E Mooser; Peter Vollenweider; Karen A Kapur; John Chambers; Nicholas J Wareham; Claudia Langenberg; Rune Frants; Ko Willems-Vandijk; Ben A Oostra; Sara M Willems; Claudia Lamina; Thomas W Winkler; Bruce M Psaty; Russell P Tracy; Jennifer Brody; Ida Chen; Jorma Viikari; Mika Kähönen; Peter P Pramstaller; David M Evans; Beate St Pourcain; Naveed Sattar; Andrew R Wood; Stefania Bandinelli; Olga D Carlson; Josephine M Egan; Stefan Böhringer; Diana van Heemst; Lyudmyla Kedenko; Kati Kristiansson; Marja-Liisa Nuotio; Britt-Marie Loo; Tamara Harris; Melissa Garcia; Alka Kanaya; Margot Haun; Norman Klopp; H-Erich Wichmann; Panos Deloukas; Efi Katsareli; David J Couper; Bruce B Duncan; Margreet Kloppenburg; Linda S Adair; Judith B Borja; James G Wilson; Solomon Musani; Xiuqing Guo; Toby Johnson; Robert Semple; Tanya M Teslovich; Matthew A Allison; Susan Redline; Sarah G Buxbaum; Karen L Mohlke; Ingrid Meulenbelt; Christie M Ballantyne; George V Dedoussis; Frank B Hu; Yongmei Liu; Bernhard Paulweber; Timothy D Spector; P Eline Slagboom; Luigi Ferrucci; Antti Jula; Markus Perola; Olli Raitakari; Jose C Florez; Veikko Salomaa; Johan G Eriksson; Timothy M Frayling; Andrew A Hicks; Terho Lehtimäki; George Davey Smith; David S Siscovick; Florian Kronenberg; Cornelia van Duijn; Ruth J F Loos; Dawn M Waterworth; James B Meigs; Josee Dupuis; J Brent Richards; Benjamin F Voight; Laura J Scott; Valgerdur Steinthorsdottir; Christian Dina; Ryan P Welch; Eleftheria Zeggini; Cornelia Huth; Yurii S Aulchenko; Gudmar Thorleifsson; Laura J McCulloch; Teresa Ferreira; Harald Grallert; Najaf Amin; Guanming Wu; Cristen J Willer; Soumya Raychaudhuri; Steve A McCarroll; Oliver M Hofmann; Ayellet V Segrè; Mandy van Hoek; Pau Navarro; Kristin Ardlie; Beverley Balkau; Rafn Benediktsson; Amanda J Bennett; Roza Blagieva; Eric Boerwinkle; Lori L Bonnycastle; Kristina Bengtsson Boström; Bert Bravenboer; Suzannah Bumpstead; Noël P Burtt; Guillaume Charpentier; Peter S Chines; Marilyn Cornelis; Gabe Crawford; Alex S F Doney; Katherine S Elliott; Amanda L Elliott; Michael R Erdos; Caroline S Fox; Christopher S Franklin; Martha Ganser; Christian Gieger; Niels Grarup; Todd Green; Simon Griffin; Christopher J Groves; Candace Guiducci; Samy Hadjadj; Neelam Hassanali; Christian Herder; Bo Isomaa; Anne U Jackson; Paul R V Johnson; Torben Jørgensen; Wen H L Kao; Augustine Kong; Peter Kraft; Johanna Kuusisto; Torsten Lauritzen; Man Li; Aloysius Lieverse; Cecilia M Lindgren; Valeriya Lyssenko; Michel Marre; Thomas Meitinger; Kristian Midthjell; Mario A Morken; Narisu Narisu; Peter Nilsson; Katharine R Owen; Felicity Payne; Ann-Kristin Petersen; Carl Platou; Christine Proença; Inga Prokopenko; Wolfgang Rathmann; N William Rayner; Neil R Robertson; Ghislain Rocheleau; Michael Roden; Michael J Sampson; Richa Saxena; Beverley M Shields; Peter Shrader; Gunnar Sigurdsson; Thomas Sparsø; Klaus Strassburger; Heather M Stringham; Qi Sun; Amy J Swift; Barbara Thorand; Jean Tichet; Tiinamaija Tuomi; Rob M van Dam; Timon W van Haeften; Thijs van Herpt; Jana V van Vliet-Ostaptchouk; G Bragi Walters; Michael N Weedon; Cisca Wijmenga; Jacqueline Witteman; Richard N Bergman; Stephane Cauchi; Francis S Collins; Anna L Gloyn; Ulf Gyllensten; Torben Hansen; Winston A Hide; Graham A Hitman; Albert Hofman; David J Hunter; Kristian Hveem; Markku Laakso; Andrew D Morris; Colin N A Palmer; Igor Rudan; Eric Sijbrands; Lincoln D Stein; Jaakko Tuomilehto; Andre Uitterlinden; Mark Walker; Richard M Watanabe; Goncalo R Abecasis; Bernhard O Boehm; Harry Campbell; Mark J Daly; Andrew T Hattersley; Oluf Pedersen; Inês Barroso; Leif Groop; Rob Sladek; Unnur Thorsteinsdottir; James F Wilson; Thomas Illig; Philippe Froguel; Cornelia M van Duijn; Kari Stefansson; David Altshuler; Michael Boehnke; Mark I McCarthy; Nicole Soranzo; Eleanor Wheeler; Nicole L Glazer; Nabila Bouatia-Naji; Reedik Mägi; Joshua Randall; Paul Elliott; Denis Rybin; Abbas Dehghan; Jouke Jan Hottenga; Kijoung Song; Anuj Goel; Taina Lajunen; Alex Doney; Christine Cavalcanti-Proença; Meena Kumari; Nicholas J Timpson; Carina Zabena; Erik Ingelsson; Ping An; Jeffrey O'Connell; Jian'an Luan; Amanda Elliott; Steven A McCarroll; Rosa Maria Roccasecca; François Pattou; Praveen Sethupathy; Yavuz Ariyurek; Philip Barter; John P Beilby; Yoav Ben-Shlomo; Sven Bergmann; Murielle Bochud; Amélie Bonnefond; Knut Borch-Johnsen; Yvonne Böttcher; Eric Brunner; Suzannah J Bumpstead; Yii-Der Ida Chen; Peter Chines; Robert Clarke; Lachlan J M Coin; Matthew N Cooper; Laura Crisponi; Ian N M Day; Eco J C de Geus; Jerome Delplanque; Annette C Fedson; Antje Fischer-Rosinsky; Nita G Forouhi; Maria Grazia Franzosi; Pilar Galan; Mark O Goodarzi; Jürgen Graessler; Scott Grundy; Rhian Gwilliam; Göran Hallmans; Naomi Hammond; Xijing Han; Anna-Liisa Hartikainen; Caroline Hayward; Simon C Heath; Serge Hercberg; David R Hillman; Aroon D Hingorani; Jennie Hui; Joe Hung; Marika Kaakinen; Jaakko Kaprio; Y Antero Kesaniemi; Mika Kivimaki; Beatrice Knight; Seppo Koskinen; Peter Kovacs; Kirsten Ohm Kyvik; G Mark Lathrop; Debbie A Lawlor; Olivier Le Bacquer; Cécile Lecoeur; Yun Li; Robert Mahley; Massimo Mangino; María Teresa Martínez-Larrad; Jarred B McAteer; Ruth McPherson; Christa Meisinger; David Melzer; David Meyre; Braxton D Mitchell; Sutapa Mukherjee; Silvia Naitza; Matthew J Neville; Marco Orrù; Ruth Pakyz; Giuseppe Paolisso; Cristian Pattaro; Daniel Pearson; John F Peden; Nancy L Pedersen; Andreas F H Pfeiffer; Irene Pichler; Ozren Polasek; Danielle Posthuma; Simon C Potter; Anneli Pouta; Michael A Province; Nigel W Rayner; Kenneth Rice; Samuli Ripatti; Fernando Rivadeneira; Olov Rolandsson; Annelli Sandbaek; Manjinder Sandhu; Serena Sanna; Avan Aihie Sayer; Paul Scheet; Udo Seedorf; Stephen J Sharp; Beverley Shields; Gunnar Sigurðsson; Eric J G Sijbrands; Angela Silveira; Laila Simpson; Andrew Singleton; Nicholas L Smith; Ulla Sovio; Amy Swift; Holly Syddall; Ann-Christine Syvänen; Anke Tönjes; André G Uitterlinden; Ko Willems van Dijk; Dhiraj Varma; Sophie Visvikis-Siest; Veronique Vitart; Nicole Vogelzangs; Gérard Waeber; Peter J Wagner; Andrew Walley; Kim L Ward; Hugh Watkins; Sarah H Wild; Gonneke Willemsen; Jaqueline C M Witteman; John W G Yarnell; Diana Zelenika; Björn Zethelius; Guangju Zhai; Jing Hua Zhao; M Carola Zillikens; Ingrid B Borecki; Pierre Meneton; Patrik K E Magnusson; David M Nathan; Gordon H Williams; Kaisa Silander; Stefan R Bornstein; Peter Schwarz; Joachim Spranger; Fredrik Karpe; Alan R Shuldiner; Cyrus Cooper; Manuel Serrano-Ríos; Lars Lind; Lyle J Palmer; Frank B Hu; Paul W Franks; Shah Ebrahim; Michael Marmot; W H Linda Kao; Peter Paul Pramstaller; Alan F Wright; Michael Stumvoll; Anders Hamsten; Thomas A Buchanan; Timo T Valle; Jerome I Rotter; Brenda W J H Penninx; Dorret I Boomsma; Antonio Cao; Angelo Scuteri; David Schlessinger; Manuela Uda; Aimo Ruokonen; Marjo-Riitta Jarvelin; Leena Peltonen; Vincent Mooser; Robert Sladek; Kiran Musunuru; Albert V Smith; Andrew C Edmondson; Ioannis M Stylianou; Masahiro Koseki; James P Pirruccello; Daniel I Chasman; Christopher T Johansen; Sigrid W Fouchier; Gina M Peloso; Maja Barbalic; Sally L Ricketts; Joshua C Bis; Mary F Feitosa; Marju Orho-Melander; Olle Melander; Xiaohui Li; Mingyao Li; Yoon Shin Cho; Min Jin Go; Young Jin Kim; Jong-Young Lee; Taesung Park; Kyunga Kim; Xueling Sim; Rick Twee-Hee Ong; Damien C Croteau-Chonka; Leslie A Lange; Joshua D Smith; Andreas Ziegler; Weihua Zhang; Robert Y L Zee; John B Whitfield; John R Thompson; Ida Surakka; Tim D Spector; Johannes H Smit; Juha Sinisalo; James Scott; Juha Saharinen; Chiara Sabatti; Lynda M Rose; Robert Roberts; Mark Rieder; Alex N Parker; Guillaume Pare; Christopher J O'Donnell; Markku S Nieminen; Deborah A Nickerson; Grant W Montgomery; Wendy McArdle; David Masson; Nicholas G Martin; Fabio Marroni; Gavin Lucas; Robert Luben; Marja-Liisa Lokki; Guillaume Lettre; Lenore J Launer; Edward G Lakatta; Reijo Laaksonen; Kirsten O Kyvik; Inke R König; Kay-Tee Khaw; Lee M Kaplan; Åsa Johansson; A Cecile J W Janssens; Wilmar Igl; G Kees Hovingh; Christian Hengstenberg; Aki S Havulinna; Nicholas D Hastie; Tamara B Harris; Talin Haritunians; Alistair S Hall; Leif C Groop; Elena Gonzalez; Nelson B Freimer; Jeanette Erdmann; Kenechi G Ejebe; Angela Döring; Anna F Dominiczak; Serkalem Demissie; Panagiotis Deloukas; Ulf de Faire; Gabriel Crawford; Yii-der I Chen; Mark J Caulfield; S Matthijs Boekholdt; Themistocles L Assimes; Thomas Quertermous; Mark Seielstad; Tien Y Wong; E-Shyong Tai; Alan B Feranil; Christopher W Kuzawa; Herman A Taylor; Stacey B Gabriel; Hilma Holm; Vilmundur Gudnason; Ronald M Krauss; Jose M Ordovas; Patricia B Munroe; Jaspal S Kooner; Alan R Tall; Robert A Hegele; John J P Kastelein; Eric E Schadt; David P Strachan; Muredach P Reilly; Nilesh J Samani; Heribert Schunkert; L Adrienne Cupples; Manjinder S Sandhu; Paul M Ridker; Daniel J Rader; Sekar Kathiresan Journal: PLoS Genet Date: 2012-03-29 Impact factor: 5.917
Authors: Aline Renata Pavan; Gabriel Dalio Bernardes da Silva; Daniela Hartmann Jornada; Diego Eidy Chiba; Guilherme Felipe Dos Santos Fernandes; Chung Man Chin; Jean Leandro Dos Santos Journal: Nutrients Date: 2016-11-10 Impact factor: 5.717