title: Inhibition of NF- κ B by Dehydroxymethylepoxyquinomicin Suppresses Invasion and Synergistically Potentiates Temozolomide and γ -Radiation Cytotoxicity in Glioblastoma Cells.
abstract: Despite advances in neurosurgery and aggressive treatment with temozolomide (TMZ) and radiation, the overall survival of patients with glioblastoma (GBM) remains poor. Vast evidence has indicated that the nuclear factor NF- κ B is constitutively activated in cancer cells, playing key roles in growth and survival. Recently, Dehydroxymethylepoxyquinomicin (DHMEQ) has shown to be a selective NF- κ B inhibitor with antiproliferative properties in GBM. In the present study, the ability of DHMEQ to surmount tumor's invasive nature and therapy resistance were further explored. Corroborating results showed that DHMEQ impaired cell growth in dose- and time-dependent manners with G2/M arrest when compared with control. Clonogenicity was also significantly diminished with increased apoptosis, though necrotic cell death was also observed at comparable levels. Notably, migration and invasion were inhibited accordingly with lowered expression of invasion-related genes. Moreover, concurrent combination with TMZ synergistically inhibited cell growth in all cell lines, as determined by proliferation and caspase-3 activation assays, though in those that express O(6)-methylguanine-DNA methyltransferase, the synergistic effects were schedule dependent. Pretreatment with DHMEQ equally sensitized cells to ionizing radiation. Taken together, our results strengthen the potential usefulness of DHMEQ in future therapeutic strategies for tumors that do not respond to conventional approaches.
authors.affiliation: Department of Pediatrics, Faculty of Medicine of Ribeirão Preto, University of São Paulo, Brazil ; Laboratório de Pediatria, Hospital das Clínicas da Faculdade de Medicina de Ribeirão Preto (USP), Bloco G, Avenida Bandeirantes, 3900 Bairro Monte Alegre, 14048-900 Ribeirão Preto, SP, Brazil.
authors.forename: M S
authors.initials: MS
authors.lastname: Brassesco
authors.forename: G M
authors.initials: GM
authors.lastname: Roberto
authors.forename: A G
authors.initials: AG
authors.lastname: Morales
authors.forename: J C
authors.initials: JC
authors.lastname: Oliveira
authors.forename: L E A
authors.initials: LE
authors.lastname: Delsin
authors.forename: J A
authors.initials: JA
authors.lastname: Pezuk
authors.forename: E T
authors.initials: ET
authors.lastname: Valera
authors.forename: C G
authors.initials: CG
authors.lastname: Carlotti
authors.forename: E M
authors.initials: EM
authors.lastname: Rego
authors.forename: H F
authors.initials: HF
authors.lastname: de Oliveira
authors.forename: C A
authors.initials: CA
authors.lastname: Scrideli
authors.forename: K
authors.initials: K
authors.lastname: Umezawa
authors.forename: L G
authors.initials: LG
authors.lastname: Tone