Antiproliferative and apoptotic effect of ascorbyl stearate in human glioblastoma multiforme cells: modulation of insulin-like growth factor-I receptor (IGF-IR) expression.
Human glioblastomas (gliomas) are characterized as highly invasive and rapidly growing brain tumors. In this study, we present data on in vitro effect of ascorbyl stearate (Asc-S), a liphophilic derivative of ascorbic acid on cell proliferation, transformation, apoptosis and modulation of expression of insulin-like growth factor-I receptor (IGF-IR) in human glioblastoma multiforme (T98G) cells. Asc-S showed significant inhibition of fetal bovine serum and human recombinant insulin-like growth factor-I (IGF-I) dependent cell proliferation in a dose dependent manner. Treatment of T98G cells with 0, 50, 100 and 150 microM Asc-S for 24h slowed down the cell multiplication cycle with significant accumulation of cells at late S/G2-M phase of cycle. Asc-S treatment (100 microM) reversed the transformed phenotype as determined by clonogenecity in soft agar and also induced apoptosis of T98G. These changes were found to be associated with significant decrease in IGF-IR expression in dose and time dependent manner compared to untreated controls. The data clearly demonstrate that Asc-S has antiproliferative and apoptotic effect on T98G cells probably through modulation of IGF-IR expression and consequent facilitation of programmed cell death.
Naidu
K A
KA
Department of Neurology, H. Lee Moffitt Cancer Center and Research Institute, College of Medicine, University of South Florida, Tampa, USA. kamathan@baylordallas.edu
Tang
J L
JL
Naidu
K A
KA
Prockop
L D
LD
Nicosia
S V
SV
Coppola
D
D
D000362:Agar; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001205:Ascorbic Acid / Q000031:analogs & derivatives* / Q000494:pharmacology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002999:Clone Cells; D003470:Culture Media; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy* / Q000235:genetics* / Q000473:pathology; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D017526:Receptor, IGF Type 1 / Q000096:biosynthesis / Q000235:genetics*
D000970:Antineoplastic Agents; D003470:Culture Media; C036225:ascorbyl monostearate; D000362:Agar; D017526:Receptor, IGF Type 1; D001205:Ascorbic Acid