PMID- 12445863
OWN - NLM
STAT- MEDLINE
DCOM- 20030116
LR  - 20220225
IS  - 0006-2952 (Print)
IS  - 0006-2952 (Linking)
VI  - 64
IP  - 12
DP  - 2002 Dec 15
TI  - Hypoxia increases tumor cell sensitivity to glycolytic inhibitors: a strategy for 
      solid tumor therapy (Model C).
PG  - 1745-51
AB  - Previously, we reported that two distinct in vitro tumor cell models of hypoxia 
      (Models A and B) are hypersensitive to glycolytic inhibitors such as 
      2-deoxy-D-glucose (2-DG) and oxamate [Liu et al., Biochemistry 2001;40:5542-7]. 
      Model A consists of osteosarcoma cells (143B) treated with agents that interfere 
      with mitochondrial oxidative phosphorylation (OxPhos), and Model B represents 
      rho(0) cells, a variant derived from 143B cells, which, due to their deficiency 
      in mitochondrial DNA, cannot perform OxPhos. Extending these studies, we report 
      here on Model C, which is composed of 143B cells grown under various levels of 
      external O(2) (0, 0.1, 0.5, 1, 5, 10, and 21%). At the lower levels of O(2) that 
      we tested, 143B cells were hypersensitive to 2-DG and oxamate when compared with 
      cells grown at a normal level of O(2). In contrast, 143B cells under hypoxic or 
      aerobic conditions showed equal sensitivity to a standard chemotherapeutic agent, 
      vinblastine. Furthermore, when treated under reduced O(2) amounts, rho(0) cells 
      displayed no hypersensitivity to 2-DG and, in fact, were slightly more resistant 
      than under aerobic conditions. At 0-5% O(2) levels, untreated 143B cells 
      displayed reduced growth and elevated lactic acid levels, while rho(0) cell 
      growth remained unaffected except at 0% O(2) where growth was inhibited by 19%. 
      The results with Model C are in agreement with our previous data using Models A 
      and B, and extend these studies by illustrating that within a wide range of 
      hypoxia the growth of tumor cells is retarded and that these slow-growing cells 
      become hypersensitized to glycolytic inhibitors. Taken together with Models A and 
      B, the data with Model C support our hypothesis that the hypoxic environment of 
      slow-growing cells found in the inner core of solid tumors renders them amenable 
      to selective targeting with glycolytic inhibitors.
CI  - Copyright 2002 Elsevier Science Inc.
FAU - Liu, Huaping
AU  - Liu H
AD  - Department of Cell Biology and Anatomy (R-124), and Sylvester Comprehensive 
      Cancer Center, University of Miami, School of Medicine, PO Box 016960, Miami, FL 
      33101, USA.
FAU - Savaraj, Niramol
AU  - Savaraj N
FAU - Priebe, Waldemar
AU  - Priebe W
FAU - Lampidis, Theodore J
AU  - Lampidis TJ
LA  - eng
GR  - CA37109-13/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Biochem Pharmacol
JT  - Biochemical pharmacology
JID - 0101032
RN  - 0 (Antimetabolites)
RN  - 0 (Insect Repellents)
RN  - 0 (Organic Chemicals)
RN  - 33X04XA5AT (Lactic Acid)
RN  - 66257-53-2 (oxamate (repellent))
RN  - 9G2MP84A8W (Deoxyglucose)
RN  - S88TT14065 (Oxygen)
SB  - IM
MH  - Antimetabolites/*pharmacology
MH  - Cell Division/drug effects
MH  - Cell Hypoxia
MH  - Deoxyglucose/*pharmacology
MH  - Humans
MH  - Insect Repellents/*pharmacology
MH  - Lactic Acid/metabolism
MH  - Organic Chemicals
MH  - Oxygen/*metabolism
MH  - Tumor Cells, Cultured
EDAT- 2002/11/26 04:00
MHDA- 2003/01/17 04:00
CRDT- 2002/11/26 04:00
PHST- 2002/11/26 04:00 [pubmed]
PHST- 2003/01/17 04:00 [medline]
PHST- 2002/11/26 04:00 [entrez]
AID - S0006295202014569 [pii]
AID - 10.1016/s0006-2952(02)01456-9 [doi]
PST - ppublish
SO  - Biochem Pharmacol. 2002 Dec 15;64(12):1745-51. doi: 
      10.1016/s0006-2952(02)01456-9.