Heat shock induces centrosomal dysfunction, and causes non-apoptotic mitotic catastrophe in human tumour cells

Abstract

Normal human diploid cells and various human tumour cells were heat shocked at 43°C for 2h and allowed to recover at 37°C. It was found that heat shock treatment transiently disrupted the immunostaining of centrosomes, and no centrosome staining was detected in either normal or tumour cells 24h after heat shock. Staining recovered thereafter in normal cells, but in tumour cells abnormal centrosomes, multiple and minute centrosomes were induced. While normal cells were arrested in G1 and G2 after heat shock, significant numbers of mitotic cells with multiple poles appeared in tumour cells. Subsequently, cells with multiple micronuclei increased in tumour cells with time after heat shock. Although the nuclear morphology of these cells was similar to that of the apoptotic cells, no DNA ladder formation was observed up to 4 days after heat shock. Furthermore, an in situ assay failed to detect signals representative of apoptosis, indicating that apoptosis did not appear to be involved in heat shock-induced cell death of human tumour cells. Instead, cell lethality was associated with mitotic catastrophe.