title: The impact of dietary isoflavonoids on malignant brain tumors.
abstract: Poor prognosis and limited therapeutic options render malignant brain tumors one of the most devastating diseases in clinical medicine. Current treatment strategies attempt to expand the therapeutic repertoire through the use of multimodal treatment regimens. It is here that dietary fibers have been recently recognized as a supportive natural therapy in augmenting the body's response to tumor growth. Here, we investigated the impact of isoflavonoids on primary brain tumor cells. First, we treated glioma cell lines and primary astrocytes with various isoflavonoids and phytoestrogens. Cell viability in a dose-dependent manner was measured for biochanin A (BCA), genistein (GST), and secoisolariciresinol diglucoside (SDG). Dose-response action for the different isoflavonoids showed that BCA is highly effective on glioma cells and nontoxic for normal differentiated brain tissues. We further investigated BCA in ex vivo and in vivo experimentations. Organotypic brain slice cultures were performed and treated with BCA. For in vivo experiments, BCA was intraperitoneal injected in tumor-implanted Fisher rats. Tumor size and edema were measured and quantified by magnetic resonance imaging (MRI) scans. In vascular organotypic glioma brain slice cultures (VOGIM) we found that BCA operates antiangiogenic and neuroprotective. In vivo MRI scans demonstrated that administered BCA as a monotherapy was effective in reducing significantly tumor-induced brain edema and showed a trend for prolonged survival. Our results revealed that dietary isoflavonoids, in particular BCA, execute toxicity toward glioma cells, antiangiogenic, and coevally neuroprotective properties, and therefore augment the range of state-of-the-art multimodal treatment approach.
authors.affiliation: Department of Neurosurgery, Erlangen University Medical School, Friedrich Alexander University Erlangen-Nuremberg (FAU), Schwabachanlage 6 (Kopfklinik), D-91054, Erlangen, Germany.
authors.forename: Tina
authors.initials: T
authors.lastname: Sehm
authors.forename: Zheng
authors.initials: Z
authors.lastname: Fan
authors.forename: Ruth
authors.initials: R
authors.lastname: Weiss
authors.forename: Marc
authors.initials: M
authors.lastname: Schwarz
authors.forename: Tobias
authors.initials: T
authors.lastname: Engelhorn
authors.forename: Nirjhar
authors.initials: N
authors.lastname: Hore
authors.forename: Arnd
authors.initials: A
authors.lastname: Doerfler
authors.forename: Michael
authors.initials: M
authors.lastname: Buchfelder
authors.forename: Iiker Y
authors.initials: IY
authors.lastname: Eyüpoglu
authors.forename: Nic E
authors.initials: NE
authors.lastname: Savaskan
mesh_terms: D000284:Administration, Oral; D020533:Angiogenesis Inhibitors / Q000008:administration & dosage* / Q000494:pharmacology; D000818:Animals; D001253:Astrocytes / Q000187:drug effects / Q000502:physiology; D001932:Brain Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D002470:Cell Survival / Q000187:drug effects; D004032:Diet; D004354:Drug Screening Assays, Antitumor; D019833:Genistein / Q000008:administration & dosage* / Q000494:pharmacology; D005910:Glioma / Q000188:drug therapy*; D006801:Humans; D008297:Male; D009368:Neoplasm Transplantation; D011916:Rats, Inbred F344; D017208:Rats, Wistar
chemical_list: D020533:Angiogenesis Inhibitors; D019833:Genistein; C004541:biochanin A
keywords: Angiogenesis; experimental therapeutics; microenvironment; nutrition