M Abdul1, N Hoosein. 1. Rumbaugh-Goodwin Institute for Cancer Research, Plantation, Florida 33313, USA.
Abstract
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. MATERIALS AND 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. CONCLUSION: Further study of the usefulness of anticonvulsants in PCa therapy is warranted.
BACKGROUND: Anticonvulsants/antiepileptics inhibit high-frequency firing of action potentials that occur during an epilepticseizure, 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. MATERIALS AND 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. CONCLUSION: Further study of the usefulness of anticonvulsants in PCa therapy is warranted.
Authors: Yanning Ding; William J Brackenbury; Pinar U Onganer; Ximena Montano; Louise M Porter; Lucy F Bates; Mustafa B A Djamgoz Journal: J Cell Physiol Date: 2008-04 Impact factor: 6.384
Authors: T Nakajima; N Kubota; T Tsutsumi; A Oguri; H Imuta; T Jo; H Oonuma; M Soma; K Meguro; H Takano; T Nagase; T Nagata Journal: Br J Pharmacol Date: 2009-01-16 Impact factor: 8.739