PMID- 14980978
OWN - NLM
STAT- MEDLINE
DCOM- 20050411
LR  - 20181113
IS  - 0007-1188 (Print)
IS  - 0007-1188 (Linking)
VI  - 141
IP  - 6
DP  - 2004 Mar
TI  - Carbamoylating chemoresistance induced by cobalt pretreatment in C6 glioma cells: 
      putative roles of hypoxia-inducible factor-1.
PG  - 988-96
AB  - 1. We tested whether pretreatment of reagents known to induce hypoxia-inducible 
      factor-1 (HIF-1) may confer chemoresistance against cytotoxicity of 
      1,3-bis(2-chloroethyl)-1-nitrosourea (BCNU) to rat C6 glioma cells. We also 
      studied which cytotoxic mechanism(s) of chloroethylnitrosoureas could be 
      neutralized by cobalt preconditioning. 2. Preconditioning of rat C6 glioma cells 
      with cobalt chloride (300 microm, 2 h) induced HIF-1 binding activity based on 
      electrophoretic mobility shift assay (EMSA). Results from Western blotting 
      confirmed a heightened HIF-1alpha level upon cobalt chloride exposure (300-400 
      microm, 2 h). Cobalt chloride (300 microm) pretreatment for 2 h substantially 
      neutralized BCNU toxicity, leading to increases in glioma cell survival based on 
      MTT assay. In addition, pre-exposure of C6 cells with desferrioxamine (DFO; 400 
      microm, 3 h), an iron chelator known to activate HIF-1, also induced HIF-1 
      binding and rendered the glioma cells resistant to cytotoxicity of BCNU. 3. 
      Pre-incubation with cobalt chloride abolished the cytotoxicity of several 
      carbamoylating agents including 2-chloroethyl isocyanate and cyclohexyl 
      isocyanate, the respective carbamoylating metabolites of BCNU and 
      1-(2-chloroethyl)-3-cyclohexyl-1-nitrosourea. The protective effect of cobalt 
      exposure, however, was not observed when cells were challenged with alkylating 
      agents including temozolomide. 4. Cadmium chloride (50 microm) effectively 
      reversed cobalt-induced HIF-1 activation. Correspondingly, cadmium chloride 
      suppressed carbamoylating chemoresistance mediated by cobalt chloride 
      pretreatment. Furthermore, both double-stranded oligodeoxynucleotide (ODN) decoy 
      with HIF-1 cognate sequence and antisense phosphorothioate ODNs against 
      HIF-1alpha partially abolished the carbamoylating chemoresistance associated with 
      cobalt preconditioning. 5. Our results suggest that cobalt- or 
      DFO-preconditioning may enhance glioma carbamoylating chemoresistance that is 
      dependent, at least in part, on induction of HIF-1.
FAU - Yang, Ding-I
AU  - Yang DI
AD  - Institute of Neuroscience, Tzu Chi University, Hualien, Taiwan.
FAU - Chen, Shang-Der
AU  - Chen SD
FAU - Yang, Ya-Ting
AU  - Yang YT
FAU - Ju, Tzyh-Chwen
AU  - Ju TC
FAU - Xu, Jin-Ming
AU  - Xu JM
FAU - Hsu, Chung Y
AU  - Hsu CY
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20040223
PL  - England
TA  - Br J Pharmacol
JT  - British journal of pharmacology
JID - 7502536
RN  - 0 (Antineoplastic Agents, Alkylating)
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Hif1a protein, rat)
RN  - 0 (Hypoxia-Inducible Factor 1)
RN  - 0 (Hypoxia-Inducible Factor 1, alpha Subunit)
RN  - 0 (Iron Chelating Agents)
RN  - 0 (Neuroprotective Agents)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Oligonucleotides)
RN  - 0 (Transcription Factors)
RN  - 3G0H8C9362 (Cobalt)
RN  - EVS87XF13W (cobaltous chloride)
RN  - J06Y7MXW4D (Deferoxamine)
RN  - U68WG3173Y (Carmustine)
SB  - IM
MH  - Animals
MH  - Antineoplastic Agents, Alkylating/*pharmacology
MH  - Carmustine/*pharmacology
MH  - Cell Line, Tumor
MH  - Cell Survival/drug effects
MH  - Cobalt
MH  - DNA-Binding Proteins/antagonists & inhibitors/biosynthesis/*physiology
MH  - Deferoxamine
MH  - Down-Regulation
MH  - *Drug Resistance, Neoplasm/drug effects
MH  - Glioblastoma
MH  - Glioma
MH  - Hypoxia-Inducible Factor 1
MH  - Hypoxia-Inducible Factor 1, alpha Subunit
MH  - Iron Chelating Agents
MH  - Neuroprotective Agents
MH  - Nuclear Proteins/antagonists & inhibitors/biosynthesis/*physiology
MH  - Oligonucleotides
MH  - Rats
MH  - Transcription Factors/antagonists & inhibitors/biosynthesis/*physiology
PMC - PMC1574263
EDAT- 2004/02/26 05:00
MHDA- 2005/04/12 09:00
PMCR- 2005/03/01
CRDT- 2004/02/26 05:00
PHST- 2004/02/26 05:00 [pubmed]
PHST- 2005/04/12 09:00 [medline]
PHST- 2004/02/26 05:00 [entrez]
PHST- 2005/03/01 00:00 [pmc-release]
AID - sj.bjp.0705687 [pii]
AID - 10.1038/sj.bjp.0705687 [doi]
PST - ppublish
SO  - Br J Pharmacol. 2004 Mar;141(6):988-96. doi: 10.1038/sj.bjp.0705687. Epub 2004 
      Feb 23.