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Hyperthermia induced NFkappaB mediated apoptosis in normal human monocytes.

Hyperthermia induced NFkappaB mediated apoptosis in normal human monocytes.

Authors :
Aravindan N
Shanmugasundaram K
Natarajan M
Source :
Molecular and cellular biochemistry [Mol Cell Biochem] 2009 Jul; Vol. 327 (1-2), pp. 29-37. Date of Electronic Publication: 2009 Feb 15.
Publication Year :
2009

Abstract

Conceptual approaches of heat-induced cytotoxic effects against tumor cells must address factors affecting therapeutic index, i.e., the relative toxicity for neoplastic versus normal tissues. Accordingly, we investigated the effect of hyperthermia treatment (HT) on the induction of DNA fragmentation, apoptosis, cell-cycle distribution, NFkappaB mRNA expression, DNA-binding activity, and phosphorylation of IkappaBalpha in the normal human Mono Mac 6 (MM6) cells. For HT, cells were exposed to 43 degrees C. FACS analysis showed a 48.5% increase in apoptosis, increased S-phase fraction, and reduced G2 phase fraction after 43 degrees C treatments. EMSA analysis showed a dose-dependent inhibition of NFkappaB DNA-binding activity after HT. This HT-mediated inhibition of NFkappaB was persistent even after 48 h. Immunoblotting analysis revealed dose-dependent inhibition of IkappaBalpha phosphorylation. Similarly, RPA analysis showed that HT persistently inhibits NFkappaB mRNA. These results demonstrate that apoptosis upon HT exposure of MM6 cells is regulated by IkappaBalpha phosphorylation mediated suppression of NFkappaB.

Details

Language :
English
ISSN :
1573-4919
Volume :
327
Issue :
1-2
Database :
MEDLINE
Journal :
Molecular and cellular biochemistry
Publication Type :
Academic Journal
Accession number :
19219626
Full Text :
https://doi.org/10.1007/s11010-009-0039-z