Hsp70- and p53-reponses after heat treatment and/or X-irradiation mediate the susceptibility of hematopoietic cells to undergo apoptosis

E.H.A. Nijhuis, A.A. Poot, J. Feijen, I. Vermes* (Corresponding Author)

*Corresponding author for this work

    Research output: Contribution to journalArticleAcademicpeer-review

    9 Citations (Scopus)
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    Abstract

    Purpose: The effect of heat treatment in combination with X-irradiation was examined with regard to expression of p53, a tumor suppressor gene product, and Hsp70, a heat-shock protein, in association with the occurrence of programmed cell death (apoptosis).

    Materials and methods: Three hematopoietic cell lines (HSB2, HL60 and Kasumi-1), which differ in p53 status, were exposed to 42.5°C during one hour and/or X-radiation (total dose 8 Gy). After exposure, both mRNA and protein expression levels of Hsp70 and p53 were investigated by real-time PCR (polymerase chain reaction) and Western blotting. Apoptosis was simultaneously analyzed by observation of cell morphology as well as flowcytometric determination of Annexin V binding to phosphatidylserine and propidium iodide exclusion.

    Results: Both HL60 and HSB2 cell lines with a low p53 status and a quick response to heat treatment with Hsp70 over-expression are less susceptible to heat-induced apoptosis compared to Kasumi-1 cells with wild-type p53 protein and no Hsp70 response. The combination of first applying X-irradiation followed by heat treatment resulted in the most effective induction of apoptosis due to impairment of the Hsp70 response in all three cell lines.

    Conclusion: These results indicate that the Hsp70 response and p53 status mediate the susceptibility of hematopoietic cells to undergo heat-induced apoptosis. Therefore, these parameters can be used as markers to predict the effectiveness of hyperthermia in cancer treatment.

    Original languageEnglish
    Pages (from-to)99-105
    Number of pages7
    JournalInternational journal of radiation biology
    Volume84
    Issue number2
    DOIs
    Publication statusPublished - 2008

    Keywords

    • Apoptosis
    • Heat shock proteins
    • Heat treatment
    • p53
    • X-irradiation

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