Inhibition by anticonvulsants of prostate-specific antigen and interleukin-6 secretion by human prostate cancer cells.
BACKGROUND
Anticonvulsants/antiepileptics inhibit high-frequency firing of action potentials that occur during an epileptic seizure, by mechanisms such as blocking sodium and calcium ion conductances. High sodium channel expression has been previously associated with aggressive behavior of prostate cancer (PCa) cell lines. The anticonvulsant phenytoin is known to inhibit the secretory activity and growth of human osteoblastic cells.


METHODS
The effect of four anticonvulsants on the secretion of prostate-specific antigen (PSA) and interleukin-6 (IL-6) by human PCa cell lines (LNCaP, DU-145 and PC-3) was studied using immunoanalysis.


RESULTS
Phenytoin and carbamazepine, which inactivate voltage-gated sodium channels, inhibited the secretion of PSA by LNCaP and IL-6 by DU-145 and PC-3 cell lines. Valproate and ethosuximide, which block calcium channels, had somewhat lower antisecretory effects. The growth of the three PCa cell lines in Matrigel was inhibited by all four anticonvulsants, at clinically-relevant doses.


CONCLUSIONS
Further study of the usefulness of anticonvulsants in PCa therapy is warranted.
Abdul
M
M
Rumbaugh-Goodwin Institute for Cancer Research, Plantation, Florida 33313, USA.
Hoosein
N
N
D000927:Anticonvulsants / Q000494:pharmacology*; D002220:Carbamazepine / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D005013:Ethosuximide / Q000494:pharmacology; D006801:Humans; D008297:Male; D010672:Phenytoin / Q000494:pharmacology; D017430:Prostate-Specific Antigen / Q000037:antagonists & inhibitors*; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism*; D014407:Tumor Cells, Cultured; D014635:Valproic Acid / Q000494:pharmacology; D000093242:Interleukin-6 Inhibitors
D000927:Anticonvulsants; D002220:Carbamazepine; D005013:Ethosuximide; D010672:Phenytoin; D017430:Prostate-Specific Antigen; D014635:Valproic Acid; D000093242:Interleukin-6 Inhibitors