Isoquercitrin isolated from Hyptis fasciculata reduces glioblastoma cell proliferation and changes beta-catenin cellular localization.
Isoquercitrin isolated from the aerial parts of Hyptis fasciculata was evaluated according to its capacity to interfere with glioblastoma (Gbm) cell growth. Gbm cells were incubated with isoquercitrin, quercetin, or rutin at concentrations of 25, 50, and 100 mumol/l for 24, 48, and 72 h. Quercetin and rutin affected Gbm cell proliferation after treatment times of longer than 24 h. However, increasing concentrations of isoquercitrin inhibited 50% of Gbm cell proliferation at 24 h and further reached nearly 90% inhibition at 72 h. This effect did not affect cell morphology, cell viability, or cleaved capase-3 levels, indicating that isoquercitrin did not induce Gbm cell death. A marked reduction in cyclin D1 levels and an increase in p27 levels were observed when 100 micromol/l of isoquercitrin was added to Gbm cells. Interestingly, nuclear beta-catenin staining observed in a subpopulation of untreated Gbm cells was found in the cytoplasm after 100-micromol/l isoquercitrin treatment. Collectively, these data show that isoquercitrin reduces Gbm cell growth without inducing apoptosis, possibly by modulating the control of the cell cycle. Our data also suggest that beta-catenin-mediated signaling may be involved on the antiproliferative activity of isoquercitrin.
Amado
Nathália G
NG
Programa de Biologia Celular e do Desenvolvimento, Instituto de Ciências Biomédicas, Universidade Federal do Rio de Janeiro, Orgânica, IQ-UFRJ, Rio de Janeiro, 21949-590, Brazil.
Cerqueira
Débora M
DM
Menezes
Fabio S
FS
da Silva
Joaquim Fernando Mendes
JF
Neto
Vivaldo Moura
VM
Abreu
Jose G
JG
D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000302:isolation & purification / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D019938:Cyclin D1 / Q000187:drug effects / Q000378:metabolism; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000187:drug effects / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D005909:Glioblastoma / Q000188:drug therapy* / Q000503:physiopathology; D006801:Humans; D031331:Hyptis / Q000737:chemistry*; D011794:Quercetin / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000302:isolation & purification / Q000494:pharmacology; D012431:Rutin / Q000008:administration & dosage / Q000494:pharmacology; D013997:Time Factors; D051176:beta Catenin / Q000378:metabolism
D000972:Antineoplastic Agents, Phytogenic; D051176:beta Catenin; C016527:isoquercitrin; D019938:Cyclin D1; D050760:Cyclin-Dependent Kinase Inhibitor p27; D012431:Rutin; D011794:Quercetin