p53 status-dependent sensitization of human tumour cells to hyperthermia by plant flavonol.
OBJECTIVE
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.


METHODS
Cell lines derived from human cancers and p53-inducible cells were used. After heat treatment at 43 degrees 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 microM 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.
Hamamoto
Tomoyuki
T
Department of Hospital Pharmacy, Nagasaki University School of Medicine, Nagasaki, Japan.
Suzuki
Keiji
K
Yamauchi
Motohiro
M
Kodama
Seiji
S
Sasaki
Hitoshi
H
Watanabe
Masami
M
D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D050884:HSP72 Heat-Shock Proteins / Q000037:antagonists & inhibitors; D006801:Humans; D006979:Hyperthermia, Induced; D011794:Quercetin / Q000627:therapeutic use*; D016159:Tumor Suppressor Protein p53 / Q000502:physiology*
D050884:HSP72 Heat-Shock Proteins; D016159:Tumor Suppressor Protein p53; D011794:Quercetin