Silencing of the human microsomal glucose-6-phosphate translocase induces glioma cell death: potential new anticancer target for curcumin.
G6P translocase (G6PT) is thought to play a crucial role in transducing intracellular signaling events in brain tumor-derived cancer cells. In this report, we investigated the contribution of G6PT to the control of U-87 brain tumor-derived glioma cell survival using small interfering RNA (siRNA)-mediated suppression of G6PT. Three siRNA constructs were generated and found to suppress up to 91% G6PT gene expression. Flow cytometry analysis of propidium iodide/annexin-V-stained cells indicated that silencing the G6PT gene induced necrosis and late apoptosis. The anticancer agent curcumin, also inhibited G6PT gene expression by more than 90% and triggered U-87 glioma cells death. Overexpression of recombinant G6PT rescued the cells from curcumin-induced cell death. Targeting G6PT expression may provide a new mechanistic rationale for the action of chemopreventive drugs and lead to the development of new anti-cancer strategies.
Belkaid
Anissa
A
Laboratoire d'Oncologie Moléculaire, Département de Chimie, Centre BIOMED, Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montréal, Que., Canada H3C 3P8.
Copland
Ian B
IB
Massillon
Duna
D
Annabi
Borhane
B
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017920:Antiporters / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D003474:Curcumin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic; D020868:Gene Silencing; D005910:Glioma / Q000201:enzymology* / Q000235:genetics / Q000473:pathology*; D006801:Humans; D008861:Microsomes / Q000201:enzymology*; D009004:Monosaccharide Transport Proteins / Q000172:deficiency / Q000235:genetics* / Q000378:metabolism; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
D000970:Antineoplastic Agents; D017920:Antiporters; D009004:Monosaccharide Transport Proteins; D011994:Recombinant Proteins; C503531:SLC37A4 protein, human; D003474:Curcumin