Thermosensitization by step-down heating in M-14 human melanoma cells

A. Delpino, A. Nista, A. M. Mileo, E. Mattei, M. Fanuele, U. Ferrini

Research output: Contribution to journalArticlepeer-review


The step-down heating (SDH) is a procedure consisting of an initial brief ''conditioning'' treatment (usually performed at temperatures above 43°C) followed immediately by a further exposure to lower temperatures (40-42°C), for extended time-periods. In this study, the effectiveness was evaluated of various SDH regimens on a human melanoma cell line (M-14). Survival tests, performed by the colony-forming assay, demonstrated that these cells, when subjected to a unique hyperthermic exposure, display a very high intrinsic thermoresistance. However, when the cells were subjected to a SDH treatment (20 min at 44°C, followed by 8 hrs at 40°C), a synergistic effect was observed. This behavior is demonstrated by the fact that the final cell survival resulted much lower than that expected on the basis of a simple additive effect of the two hyperthermic treatments. A synergistic effect was also obtained when the cultures were exposed to SDH regimens consisting of two very mild and rather ineffective treatments (42°C for 1 hr, followed by reincubation at 40°C for 8 to 16 hrs). The effectiveness of SDH procedures was confirmed by observations performed with fluorescence microscopy, by using a fluorescent dye (the dansyl lysine) that selectively stains heat-damaged cells. These results suggest that the SDH procedure must be regarded as a promising tool for enhancing the effectiveness of clinical treatments of human cancers based on hyperthermia.

Original languageEnglish
Pages (from-to)71-78
Number of pages8
JournalJournal of Experimental and Clinical Cancer Research
Issue number2
Publication statusPublished - 1990

ASJC Scopus subject areas

  • Cancer Research
  • Oncology


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