title: Graphene Functionalized with Arginine Decreases the Development of Glioblastoma Multiforme Tumor in a Gene-Dependent Manner.
abstract: Our previous studies revealed that graphene had anticancer properties in experiments in vitro with glioblastoma multiforme (GBM) cells and in tumors cultured in vivo. We hypothesized that the addition of arginine or proline to graphene solutions might counteract graphene agglomeration and increase the activity of graphene. Experiments were performed in vitro with GBM U87 cells and in vivo with GBM tumors cultured on chicken embryo chorioallantoic membranes. The measurements included cell morphology, mortality, viability, tumor morphology, histology, and gene expression. The cells and tumors were treated with reduced graphene oxide (rGO) and rGO functionalized with arginine (rGO + Arg) or proline (rGO + Pro). The results confirmed the anticancer effect of graphene on GBM cells and tumor tissue. After functionalization with amino acids, nanoparticles were distributed more specifically, and the flakes of graphene were less agglomerated. The molecule of rGO + Arg did not increase the expression of TP53 in comparison to rGO, but did not increase the expression of MDM2 or the MDM2/TP53 ratio in the tumor, suggesting that arginine may block MDM2 expression. The expression of NQO1, known to be a strong protector of p53 protein in tumor tissue, was greatly increased. The results indicate that the complex of rGO + Arg has potential in GBM therapy.
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. ewa_sawosz@sggw.pl.
authors.forename: Ewa
authors.initials: E
authors.lastname: Sawosz
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. jaworski.slawek@gmail.com.
authors.forename: Sławomir
authors.initials: S
authors.lastname: Jaworski
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. marta_prasek@sggw.pl.
authors.forename: Marta
authors.initials: M
authors.lastname: Kutwin
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg 1870, Denmark. krish@sund.ku.dk.
authors.forename: Krishna Prasad
authors.initials: KP
authors.lastname: Vadalasetty
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. mgrodka@gmail.com.
authors.forename: Marta
authors.initials: M
authors.lastname: Grodzik
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. mateusz.wierzbicki1@gmail.com.
authors.forename: Mateusz
authors.initials: M
authors.lastname: Wierzbicki
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. natalia.kurantowicz@gmail.com.
authors.forename: Natalia
authors.initials: N
authors.lastname: Kurantowicz
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. barb.strojny@gmail.com.
authors.forename: Barbara
authors.initials: B
authors.lastname: Strojny
authors.affiliation: Department of Animal Nutrition and Biotechnology, Warsaw University of Life Sciences, Warsaw 02-787, Poland. anna_hotowy@sggw.pl.
authors.forename: Anna
authors.initials: A
authors.lastname: Hotowy
authors.affiliation: Institute of Electronic Materials Technology, Warsaw 02-787, Poland. ludwika.lipinska2008@gmail.com.
authors.forename: Ludwika
authors.initials: L
authors.lastname: Lipińska
authors.affiliation: Institute of Electronic Materials Technology, Warsaw 02-787, Poland. joanna.jagiello@itme.edu.pl.
authors.forename: Joanna
authors.initials: J
authors.lastname: Jagiełło
authors.affiliation: Department of Veterinary Clinical and Animal Sciences, University of Copenhagen, Frederiksberg 1870, Denmark. ach@sund.ku.dk.
authors.forename: André
authors.initials: A
authors.lastname: Chwalibog
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D001120:Arginine / Q000737:chemistry; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival; D002642:Chick Embryo; D005909:Glioblastoma / Q000378:metabolism*; D006108:Graphite / Q000737:chemistry / Q000494:pharmacology*; D016660:NAD(P)H Dehydrogenase (Quinone) / Q000235:genetics / Q000378:metabolism; D009474:Neurons / Q000187:drug effects; D010087:Oxides / Q000737:chemistry; D051736:Proto-Oncogene Proteins c-mdm2 / Q000235:genetics / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; D010087:Oxides; D016159:Tumor Suppressor Protein p53; D006108:Graphite; D001120:Arginine; D016660:NAD(P)H Dehydrogenase (Quinone); C447479:NQO1 protein, human; C497206:MDM2 protein, human; D051736:Proto-Oncogene Proteins c-mdm2
keywords: amino acids; cells; gene expression; glioblastoma multiforme; graphene; reduced graphene oxide; tumor