Cyclocreatine transport and cytotoxicity in rat glioma and human
ovarian carcinoma cells: 31p nmr spectroscopy .
Schiffenbauer, Yael S., Gila Meir, #mildred Cohn, and Michal Neeman.
Department of Hormone Research, Weizmann Institute of Science,
Rehovot 76100, ISRAEL and Department of Biochemistry and Biophysics,
University of Pennsylvania, Philadelphia PA 19104-6089 USA
APStracts 2:0291C, 1995.
Cyclocreatine (CY), an analogue of creatine, inhibits tumor growth in
vivo and proliferation of tumor cells in vitro. The goal of this
study was to probe the mechanism of CY transport and cytotoxicity in
C6 rat glioma cells and OC238 human ovarian carcinoma cells (creatine
kinase activities of 0.16 and 0.016 units/mg protein respectively).
In both cell lines CY significantly inhibited cell growth with no
effect on membrane integrity and on the content of nucleoside
triphosphates. An intrinsic 31P-NMR signal of phosphocreatine, as
well as accumulation of phosphocyclocreatine (PCY) after addition of
CY, was observed for C6 glioma but not for the OC238 cells. Transport
of CY in C6 glioma showed Michaelis-Menten kinetics for an active
sodium-dependent component. Transport was reduced more than 5 fold in
low glucose medium. The toxicity of CY to C6 glioma cells may be due
to PCY accumulation and cellular swelling. Another mechanism must be
invoked to explain CY effects on the human ovarian cancer cells in
which no PCY accumulation could be detected and no cellular swelling
was observed.
Received 15 February 1995; accepted in final form 26 July 1995.
APS Manuscript Number C87-5.
Article publication pending Am. J. Physiol. (Cell Physiology).
ISSN 1080-4757 Copyright 1995 The American Physiological Society.
Published in APStracts on 14 August 1995.