Modulation of the HSV-TK/ganciclovir bystander effect by n-butyrate in glioblastoma: correlation with gap-junction intercellular communication.
The efficacy of HSV-TK/ganciclovir gene therapy largely relies on the bystander effect, i.e. the ability of transfected cells to kill the adjacent, untrasfected cells. This mechanism itself depends chiefly on the transfer via gap junctions of phosphorylated ganciclovir between cells, and is often deficient in glioblastomas. In this report, we demonstrate that n-butyrate markedly enhances the gap junction intercellular communication of GJIC-deficient glioma cells, and significantly increases the bystander effect in such cells. This effect of n-butyrate appears to be independent from its HDAC inhibitory effect, since trichostatin A does not reproduce it.
Robe
Pierre A
PA
Center of Molecular and Cellular Neuroscience, University of Liège, Belgium. pierre.robe@ulg.ac.be
Jolois
Olivier
O
N'Guyen
Minh
M
Princen
Frederic
F
Malgrange
Brigitte
B
Merville
Marie-Paule
MP
Bours
Vincent
V
D002087:Butyrates / Q000494:pharmacology*; D024201:Bystander Effect / Q000187:drug effects / Q000502:physiology*; D002450:Cell Communication / Q000502:physiology*; D045744:Cell Line, Tumor; D018031:Connexin 43 / Q000032:analysis; D017629:Gap Junctions / Q000502:physiology*; D005909:Glioblastoma; D006801:Humans; D018139:Simplexvirus / Q000201:enzymology*; D013937:Thymidine Kinase / Q000494:pharmacology*
D002087:Butyrates; D018031:Connexin 43; D013937:Thymidine Kinase