Inhibition of the oxidative and nonoxidative pentose phosphate pathways by somatostatin: a possible mechanism of antitumor action.
Long-acting somatostatin analogs have recently become supplemental drugs in the treatment of neurofibroma because of their marked tumor growth inhibitory effect. Somatostatin is currently under extended evaluation in other cancers as a possible supplemental drug to the treatment protocols in use. The mode of action is not known. Somatostatin has been shown to cause glucose intolerance by inhibiting glucose-6-phosphate dehydrogenase (G6PD) in fish liver. Recent data generated in our laboratory indicate that it is this pathway and the transketolase reactions of the pentose cycle (PC) which are directly involved in the ribose synthesis process of pancreatic adenocarcinoma cells. In cell culture, somatostatin alone inhibited glucose carbon recycling through the PC by 5.7%, which was increased to 19.8% in combination with oxythiamine, a competitive inhibitor of transketolase. Oxythiamine produced strong apoptosis in in-vitro hosted tumor cells. We hypothesize that somatostatin- and oxythiamine-induced antiproliferative action is mediated by the inhibition of G6PD, transketolase, or both.
The Ohio State University College of Medicine, Department of Surgery, Columbus, USA. lboros@magnus.acs.ohio-state.edu
L G
LG
Boros
J L
JL
Brandes
F I
FI
Yusuf
M
M
Cascante
R D
RD
Williams
W J
WJ
Schirmer
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002455:Cell Division / Q000187:drug effects; D005947:Glucose / Q000378:metabolism; D005954:Glucosephosphate Dehydrogenase / Q000378:metabolism; D006801:Humans; D008954:Models, Biological; D009369:Neoplasms / Q000378:metabolism*; D010085:Oxidative Phosphorylation / Q000187:drug effects*; D010427:Pentose Phosphate Pathway / Q000187:drug effects*; D013004:Somatostatin / Q000494:pharmacology*; D014174:Transketolase / Q000378:metabolism
D000970:Antineoplastic Agents; D013004:Somatostatin; D005954:Glucosephosphate Dehydrogenase; D014174:Transketolase; D005947:Glucose