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NF-kappaB inhibition impairs the radioresponse of hypoxic EMT-6 tumour cells through downregulation of inducible nitric oxide synthase.

De Ridder M, Van den Berge DL, Verovski VN, Monsaert C, Wauters N, Storme GA - Br. J. Cancer (2003)

Bottom Line: Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB).Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsine oxide and lactacystin.Contrasting to other studies, our data show that inhibition of NF-kappaB may impair the radioresponse of tumour cells through downregulation of iNOS.

View Article: PubMed Central - PubMed

Affiliation: Oncology Center, Cancer Research Unit, Academic Hospital Free University Brussels (A.Z.-V.U.B.), Laarbeeklaan 101, B 1090, Brussels, Belgium. Mark.De.Ridder@vub.ac.be

ABSTRACT
Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB). Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsine oxide and lactacystin. Contrasting to other studies, our data show that inhibition of NF-kappaB may impair the radioresponse of tumour cells through downregulation of iNOS.

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Effect of lactacystin and PAO on nitrite production by EMT-6 cells. (A) EMT-6 cultures were exposed to 0.0001–0.1 μg ml−1 LPS for 16 h in 1% oxygen and afterwards analysed for the accumulation of nitrite, with or without 3 mM aminoguanidine. (B) Nitrite production after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by exposure to 0.1 μg ml−1 LPS in 1% oxygen.
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fig3: Effect of lactacystin and PAO on nitrite production by EMT-6 cells. (A) EMT-6 cultures were exposed to 0.0001–0.1 μg ml−1 LPS for 16 h in 1% oxygen and afterwards analysed for the accumulation of nitrite, with or without 3 mM aminoguanidine. (B) Nitrite production after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by exposure to 0.1 μg ml−1 LPS in 1% oxygen.

Mentions: Effect of lactacystin and PAO on iNOS expression in hypoxic EMT-6 cells. (A) EMT-6 cultures were exposed to 0.001–0.1 μg ml−1 LPS in 1% oxygen and afterwards analysed for the expression of iNOS by Western blotting. The last lane illustrates the iNOS induction by LPS in 21% oxygen. (B, C) iNOS expression after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by a 16 h exposure to 0.1 μg ml−1 LPS in 1% oxygen. The figure is representative of four independent experiments.


NF-kappaB inhibition impairs the radioresponse of hypoxic EMT-6 tumour cells through downregulation of inducible nitric oxide synthase.

De Ridder M, Van den Berge DL, Verovski VN, Monsaert C, Wauters N, Storme GA - Br. J. Cancer (2003)

Effect of lactacystin and PAO on nitrite production by EMT-6 cells. (A) EMT-6 cultures were exposed to 0.0001–0.1 μg ml−1 LPS for 16 h in 1% oxygen and afterwards analysed for the accumulation of nitrite, with or without 3 mM aminoguanidine. (B) Nitrite production after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by exposure to 0.1 μg ml−1 LPS in 1% oxygen.
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Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC2376775&req=5

fig3: Effect of lactacystin and PAO on nitrite production by EMT-6 cells. (A) EMT-6 cultures were exposed to 0.0001–0.1 μg ml−1 LPS for 16 h in 1% oxygen and afterwards analysed for the accumulation of nitrite, with or without 3 mM aminoguanidine. (B) Nitrite production after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by exposure to 0.1 μg ml−1 LPS in 1% oxygen.
Mentions: Effect of lactacystin and PAO on iNOS expression in hypoxic EMT-6 cells. (A) EMT-6 cultures were exposed to 0.001–0.1 μg ml−1 LPS in 1% oxygen and afterwards analysed for the expression of iNOS by Western blotting. The last lane illustrates the iNOS induction by LPS in 21% oxygen. (B, C) iNOS expression after a 3 h pretreatment with lactacystin (LC) and a 10 min pretreatment with PAO followed by a 16 h exposure to 0.1 μg ml−1 LPS in 1% oxygen. The figure is representative of four independent experiments.

Bottom Line: Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB).Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsine oxide and lactacystin.Contrasting to other studies, our data show that inhibition of NF-kappaB may impair the radioresponse of tumour cells through downregulation of iNOS.

View Article: PubMed Central - PubMed

Affiliation: Oncology Center, Cancer Research Unit, Academic Hospital Free University Brussels (A.Z.-V.U.B.), Laarbeeklaan 101, B 1090, Brussels, Belgium. Mark.De.Ridder@vub.ac.be

ABSTRACT
Hypoxic EMT-6 tumour cells displayed a high level of inducible nitric oxide synthase (iNOS) and an increased radiosensitivity after a 16 h exposure to lipopolysaccharide, a known activator of nuclear factor-kappaB (NF-kappaB). Both iNOS activation and radioresponse were impaired by the NF-kappaB inhibitors phenylarsine oxide and lactacystin. Contrasting to other studies, our data show that inhibition of NF-kappaB may impair the radioresponse of tumour cells through downregulation of iNOS.

Show MeSH
Related in: MedlinePlus