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Molecular and Cellular Biochemistry

, Volume 327, Issue 1–2, pp 29–37 | Cite as

Hyperthermia induced NFκB mediated apoptosis in normal human monocytes

  • Natarajan Aravindan
  • Karthigayan Shanmugasundaram
  • Mohan Natarajan
Article

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, NFκB mRNA expression, DNA-binding activity, and phosphorylation of IκBα in the normal human Mono Mac 6 (MM6) cells. For HT, cells were exposed to 43°C. FACS analysis showed a 48.5% increase in apoptosis, increased S-phase fraction, and reduced G2 phase fraction after 43°C treatments. EMSA analysis showed a dose-dependent inhibition of NFκB DNA-binding activity after HT. This HT-mediated inhibition of NFκB was persistent even after 48 h. Immunoblotting analysis revealed dose-dependent inhibition of IκBα phosphorylation. Similarly, RPA analysis showed that HT persistently inhibits NFκB mRNA. These results demonstrate that apoptosis upon HT exposure of MM6 cells is regulated by IκBα phosphorylation mediated suppression of NFκB.

Keywords

Hyperthermia treatment NFκB DNA-binding activity Apoptosis Human monocytes Normal cells 

Notes

Acknowledgment

This research was supported by the Office of Science (BER), U.S. Department of Energy, Grant No. DE-FG02-03ER63449 and the Department of Radiation Oncology, The University of Oklahoma Health Science Center, Oklahoma City, OK, USA.

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Copyright information

© Springer Science+Business Media, LLC. 2009

Authors and Affiliations

  • Natarajan Aravindan
    • 1
  • Karthigayan Shanmugasundaram
    • 2
  • Mohan Natarajan
    • 2
  1. 1.Department of Radiation Oncology, OUPB 1430University of Oklahoma Health Sciences CenterOklahoma CityUSA
  2. 2.Department of OtolaryngologyUniversity of Texas Health Science Center at San AntonioSan AntonioUSA

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