Sodium phenylacetate (NaPa) improves the TAM effect on glioblastoma experimental tumors by inducing cell growth arrest and apoptosis.
BACKGROUND
Multiform glioblastomas represent the most aggressive brain tumors. Here, the cooperative effects of sodium phenylacetate (NaPa) and/or tamoxifen (TAM) on CNS1 and 9L glioblastoma cell lines in vitro and in an experimental animal tumor model were investigated.


METHODS
The drug effects on cell cycle and apoptosis were investigated by flow cytometry. CNS1 cells were implanted subcutaneously in nude mice to form tumors which were then treated with NaPa, TAM or NaPa/TAM.


RESULTS
A significant inhibitory effect of NaPa on the two glioma cell lines (LD50 of 10 mM) was observed. 10(-5) M of TAM inhibited approximately 35% of 9L cell growth, and 90% of CNS1 cell growth. When a combination of both drugs included 10(-9) M of TAM, inhibition of about 50% of 9L cell growth and 75% of CNS1 cell growth occurred. The NaPa/TAM combined treatment increased the number of G0/G1 arrested cells and apoptotic cells as compared to treatments with NaPa or TAM alone. Inhibition of CNS1 tumor growth were observed after a two week treatment with NaPa (32 mg/kg/day) or TAM (6 mg/kg/day).


CONCLUSIONS
These results showed a synergistic effect between these two drugs on tumor cell proliferation, caused by cell cycle arrest in the G0/G1 phase and by induction of apoptosis.
Wei
Ming X
MX
Laboratoire d'Oncologie Moléculaire et Cellulaire, SMBH, Université Paris XIII, 74 rue Marcel Cachin, 93017 Bobign, France.
Liu
Jian Miao
JM
Gadal
Franck
F
Yi
Ping
P
Liu
Jianfeng
J
Crepin
Michel
M
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D001932:Brain Neoplasms / Q000188:drug therapy* / Q000473:pathology; D048708:Cell Growth Processes / Q000187:drug effects; D045744:Cell Line, Tumor; D004357:Drug Synergism; D005260:Female; D005909:Glioblastoma / Q000188:drug therapy* / Q000473:pathology; D018316:Gliosarcoma / Q000188:drug therapy / Q000473:pathology; D051379:Mice; D008819:Mice, Nude; D010648:Phenylacetates / Q000008:administration & dosage; D051381:Rats; D013629:Tamoxifen / Q000008:administration & dosage
D010648:Phenylacetates; D013629:Tamoxifen; C025136:phenylacetic acid