Abstract
The effect of down-regulation of folylpoly-γ-glutamate synthetase (FPGS) activity on intracellular reduced folate accumulation and cellular proliferation was examined, using an inducible antisense expression system in the human T-lymphoblastic leukemia cell line CCRF-CEM. FPGS catalyzes the addition of γ-glutamyl residues to natural folates and classical antifolates, which results in their enhanced cellular retention and increased cytotoxicity. As such, this enzyme has become a focus as a potential anticancer drug target. However, direct evidence to support this concept has been elusive. Hence, a study was undertaken using an antisense-based expression system to down-regulate FPGS activity. This inducible expression system was used to demonstrate that lower FPGS activity can lead to substantially lower intracellular folate content, which coincides with suppression of thymidylate synthesis and inhibition of cellular proliferation. Copyright (C) 1998 Elsevier Science, Inc.
| Original language | English |
|---|---|
| Pages (from-to) | 2031-2037 |
| Number of pages | 7 |
| Journal | Biochemical Pharmacology |
| Volume | 55 |
| Issue number | 12 |
| DOIs | |
| State | Published - Jun 15 1998 |
| Externally published | Yes |
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Keywords
- Antisense
- Cellular proliferation
- Folylpolyglutamate synthetase
- Reduced folates
ASJC Scopus subject areas
- Pharmacology
Cite this
Effects of antisense-based folylpoly-γ-glutamate synthetase down-regulation on reduced folates and cellular proliferation in CCRF-CEM cells. / Liu, Yinong; Raghunathan, K.; Hill, Charles; He, Yunhua; Bunni, Marlene A.; Barredo, Julio; Priest, David G.
In: Biochemical Pharmacology, Vol. 55, No. 12, 15.06.1998, p. 2031-2037.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Effects of antisense-based folylpoly-γ-glutamate synthetase down-regulation on reduced folates and cellular proliferation in CCRF-CEM cells
AU - Liu, Yinong
AU - Raghunathan, K.
AU - Hill, Charles
AU - He, Yunhua
AU - Bunni, Marlene A.
AU - Barredo, Julio
AU - Priest, David G.
PY - 1998/6/15
Y1 - 1998/6/15
N2 - The effect of down-regulation of folylpoly-γ-glutamate synthetase (FPGS) activity on intracellular reduced folate accumulation and cellular proliferation was examined, using an inducible antisense expression system in the human T-lymphoblastic leukemia cell line CCRF-CEM. FPGS catalyzes the addition of γ-glutamyl residues to natural folates and classical antifolates, which results in their enhanced cellular retention and increased cytotoxicity. As such, this enzyme has become a focus as a potential anticancer drug target. However, direct evidence to support this concept has been elusive. Hence, a study was undertaken using an antisense-based expression system to down-regulate FPGS activity. This inducible expression system was used to demonstrate that lower FPGS activity can lead to substantially lower intracellular folate content, which coincides with suppression of thymidylate synthesis and inhibition of cellular proliferation. Copyright (C) 1998 Elsevier Science, Inc.
AB - The effect of down-regulation of folylpoly-γ-glutamate synthetase (FPGS) activity on intracellular reduced folate accumulation and cellular proliferation was examined, using an inducible antisense expression system in the human T-lymphoblastic leukemia cell line CCRF-CEM. FPGS catalyzes the addition of γ-glutamyl residues to natural folates and classical antifolates, which results in their enhanced cellular retention and increased cytotoxicity. As such, this enzyme has become a focus as a potential anticancer drug target. However, direct evidence to support this concept has been elusive. Hence, a study was undertaken using an antisense-based expression system to down-regulate FPGS activity. This inducible expression system was used to demonstrate that lower FPGS activity can lead to substantially lower intracellular folate content, which coincides with suppression of thymidylate synthesis and inhibition of cellular proliferation. Copyright (C) 1998 Elsevier Science, Inc.
KW - Antisense
KW - Cellular proliferation
KW - Folylpolyglutamate synthetase
KW - Reduced folates
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UR - http://www.scopus.com/inward/citedby.url?scp=0032525917&partnerID=8YFLogxK
U2 - 10.1016/S0006-2952(98)00089-6
DO - 10.1016/S0006-2952(98)00089-6
M3 - Article
C2 - 9714324
AN - SCOPUS:0032525917
VL - 55
SP - 2031
EP - 2037
JO - Biochemical Pharmacology
JF - Biochemical Pharmacology
SN - 0006-2952
IS - 12
ER -