p53 status-dependent sensitization of human tumour cells to hyperthermia by plant flavonol Tomoyuki Hamamoto a; Keiji Suzuki b; Motohiro Yamauchi b; Seiji Kodama c; Hitoshi Sasaki a; Masami Watanabe d a Department of Hospital Pharmacy, Nagasaki University School of Medicine, Nagasaki b Division of Radiation Biology, Department of Radiology and Radiation Biology, Course of Life Sciences and Radiation Research, Graduate School of Biomedical Sciences, Nagasaki University, Nagasaki c Radiation Biology Laboratory, Frontier Science Innovation Center, Organization for University-Industry-Government Cooperation, Osaka Prefecture University, Osaka d Laboratory of Radiation Biology, Division of Radiation Life Science, Kyoto University Research Reactor Institute, Osaka, Japan Abstract Purpose: Quercetin (QCT), an important flavonol, is known to sensitize tumour cells to hyperthermia by suppressing heat shock protein 72 (Hsp72) induction, and is also reported to inhibit p53 accumulation. This study was conducted to examine the effects of QCT on the heat sensitivities of human tumour cell lines with different p53 statuses. Material and methods: Cell lines derived from human cancers and p53-inducible cells were used. After heat treatment at 43°C for 2 h with or without QCT, cell survival was determined in a clonogenic assay. The cellular and nuclear content of Hsp72 as well as that of p53 was determined by Western blotting analysis. Results: Treatment of cells with 150 µM QCT, which completely abolished Hsp72 induction, potentiated the lethal effects of hyperthermia in all tumour cell lines. Particularly, remarkable enhancement of cell death was observed in tumour cell lines having little or no p53 proteins. Although nuclear translocation of Hsp72 is induced by hyperthermia, it was significantly compromised in p53-deficient cells. Conclusions: These results indicate that p53 is a component for nuclear accumulation of Hsp72; therefore, p53 status is an important determinant of the sensitization of human tumour cells to hyperthermia by QCT. International Journal of Hyperthermia, Volume 24, Issue 5 2008 , pages 415 - 424 Remember we are NOT Doctors and have NO medical training. This site is like an Encylopedia - there are many pages, many links on many topics. Support our work with any size DONATION - see left side of any page - for how to donate. You can help raise awareness of CAM.