In vitro inhibition of cell proliferation, viability, and invasiveness in U87MG human glioblastoma cells by estramustine phosphate.
OBJECTIVE
Several determinants of cell motility are highly dependent on the cytoskeleton, in particular, microtubules. To our knowledge, there have been no previous reports regarding the anti-invasive ability by an antimicro-tubule agent, estramustine phosphate (EMP), on glioblastoma cell lines. We investigated the modulated cell proliferation and invasiveness by EMP in vitro.


METHODS
We determined the relative survival rate by cell proliferation assay and the percent survival fraction by monotetrazolium assay. Furthermore, an invasion index was used to quantify the migrating and invasive potential of the human glioblastoma cell line, U87MG, in Boiden's chamber with reconstituted basement membrane (Matrigel; Collaborative Research, Lexington, MA).


RESULTS
We found that 0.5 mumol/L EMP had no effect in any of the assays. Concentrations of 1, 5, and 10 mumol/L demonstrated a concentration- and time-dependent depression in all of the assays. A range of drug concentration of EMP, 1 to 10 mumol/L, in which cell invasiveness was successfully inhibited, was comparable with antiproliferative capacity.


CONCLUSIONS
The data add to the findings that EMP not only offers selective antiproliferative activity against glioblastoma but also reduces invasiveness, consistent with its main mechanism of action. Such findings form the basis for the development of agents that use non-DNA targets for the treatment of glioblastomas and may improve control over tumor proliferation and invasion.
Yoshida
D
D
Department of Neurosurgery, Nippon Medical School, Tokyo, Japan.
Piepmeier
J M
JM
Teramoto
A
A
D018906:Antineoplastic Agents, Alkylating / Q000494:pharmacology*; D001932:Brain Neoplasms / Q000473:pathology*; D002455:Cell Division / Q000187:drug effects*; D002460:Cell Line; D002465:Cell Movement / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects*; D004305:Dose-Response Relationship, Drug; D004961:Estramustine / Q000494:pharmacology*; D005909:Glioblastoma / Q000473:pathology*; D006801:Humans; D009361:Neoplasm Invasiveness; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000473:pathology
D018906:Antineoplastic Agents, Alkylating; D004961:Estramustine