Helianthin induces antiproliferative effect on human glioblastoma cells in vitro.
A major focus of brain cancer research today is to translate understanding of glioma biology into advances in treatment, by exploring the potential of target therapy. Here we investigated the ability of three compounds belonging to the chemical class of azo dyes (methyl red, methyl yellow, and helianthin) to inhibit glioblastoma (GB) cell growth in vitro. Our results showed that helianthin induced cytotoxicity in two GB cell cultures, cell lines 18 and 38, whereas methyl red and methyl yellow were not cytotoxic. The effect of helianthin on EGFR, IGF-1R, and their common intracellular signaling via PI3-K and ERK1/2 was also analyzed. Treatment with helianthin down-regulated EGFR and IGF-1R activity in both cell lines. Helianthin treatment blocked ERK1/2 phosphorylation without affecting PI3K activity in cell line 18 and reduced both PI3K and ERK1/2 in GB 38 cell line. The cell death was accompanied by degradation of PARP without affecting BCL2 expression in both GB cell cultures. Because of the genetic heterogeneity of malignant gliomas, we tested the effect of helianthin on other two primary GB lines (11 and 15) and two early-passage GB cultures (BT1GB and BT2GB), to assess the general nature of the anti-tumor effect of the drug in GB cells. We found that helianthin treatment induced cell death in all the GB cell cultures analyzed. To our knowledge, this is the first report indicating that helianthin can reduce GB cell growth.
Alexandru
Oana
O
University of Medicine and Pharmacy, Petru Rares Street, No 2, 200349 Craiova, Romania.
Dragutescu
Laura
L
Tataranu
Ligia
L
Ciubotaru
Vasile
V
Sevastre
Ani
A
Georgescu
Ada Maria
AM
Purcaru
Oana
O
Danoiu
Suzana
S
Bäcklund
L Magnus
LM
Dricu
Anica
A
D017209:Apoptosis / Q000187:drug effects; D001391:Azo Compounds / Q000494:pharmacology; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D049109:Cell Proliferation / Q000187:drug effects*; D003064:Cnidarian Venoms / Q000494:pharmacology*; D003603:Cytotoxins / Q000494:pharmacology*; D066246:ErbB Receptors / Q000378:metabolism; D005909:Glioblastoma / Q000188:drug therapy* / Q000378:metabolism; D006801:Humans; D047468:Immunoprecipitation; D066298:In Vitro Techniques; D019950:Mitogen-Activated Protein Kinase 1 / Q000378:metabolism; D048052:Mitogen-Activated Protein Kinase 3 / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D017526:Receptor, IGF Type 1 / Q000378:metabolism; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D004124:p-Dimethylaminoazobenzene / Q000494:pharmacology
D001391:Azo Compounds; D003064:Cnidarian Venoms; D003603:Cytotoxins; C008492:methyl red; C038137:cytolysin III (Stoichactis helianthus); D004124:p-Dimethylaminoazobenzene; D019869:Phosphatidylinositol 3-Kinases; C512478:EGFR protein, human; D066246:ErbB Receptors; D017526:Receptor, IGF Type 1; C535150:MAPK1 protein, human; D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3