Boldine: a potential new antiproliferative drug against glioma cell lines.
Malignant gliomas are the most common and devastating primary tumors of the central nervous system. Currently no efficient treatment is available. This study evaluated the effect and underlying mechanisms of boldine, an aporphine alkaloid of Peumus boldus, on glioma proliferation and cell death. Boldine decreased the cell number of U138-MG, U87-MG and C6 glioma lines at concentrations of 80, 250 and 500 muM. We observed that cell death caused by boldine was cell-type specific and dose-dependent. Exposure to boldine for 24 h did not activate key mediators of apoptosis. However, it induced alterations in the cell cycle suggesting a G(2)/M arrest in U138-MG cells. Boldine had no toxic effect on non-tumor cells when used at the same concentrations as those used on tumor cells. Based on these results, we speculate that boldine may be a promising compound for evaluation as an anti-cancer agent.
Gerhardt
Daniéli
D
Programa de Pós graduação em Ciências Biológicas: Bioquímica, Departamento de Bioquímica, Instituto de Ciências Básicas da Saúde, UFRGS, Rua Ramiro Barcelos 2600, 90035.003, Porto Alegre, RS, Brazil.
Horn
Ana Paula
AP
Gaelzer
Mariana Maier
MM
Frozza
Rudimar Luiz
RL
Delgado-Cañedo
Andrés
A
Pelegrini
Alessandra Luiza
AL
Henriques
Amélia T
AT
Lenz
Guido
G
Salbego
Christianne
C
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D001060:Aporphines / Q000737:chemistry / Q000494:pharmacology* / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects / Q000473:pathology; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004249:DNA Damage; D004354:Drug Screening Assays, Antitumor; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D005910:Glioma / Q000188:drug therapy* / Q000201:enzymology / Q000473:pathology*; D006801:Humans; D066298:In Vitro Techniques; D008297:Male; D008938:Mitosis / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar
D000970:Antineoplastic Agents; D001060:Aporphines; C011686:boldine; D053148:Caspase 3; D053453:Caspase 9