Boldine enhances hyperthermia-induced apoptosis in AGS gastric cancer cells in association with attenuation of the HSF1-HSP stress response.

BACKGROUND

Gastric cancer presents therapeutic challenges owing to treatment resistance and stress adaptation. This study investigated whether boldine enhances mild hyperthermia-induced cytotoxicity in AGS gastric cancer cells and evaluated its association with attenuation of the heat shock response involving heat shock proteins (HSPs) and heat shock factor 1 (HSF1).

METHODS AND

RESULTS

AGS cells were pretreated with boldine (1 h) and exposed to 37-43 °C (30 min). Combined treatment reduced viability, wound closure, and colony formation more than single treatments. The apoptotic fraction increased from 8.08% in untreated controls to 28.79% with boldine alone and 3.55% with hyperthermia alone, reaching 46.33% after cotreatment. Cotreatment altered cell cycle distribution (S and G2/M fractions), increased reactive oxygen species (ROS) accumulation, and enhanced MAPK phosphorylation. N-acetylcysteine (NAC) pretreatment reduced ROS levels and apoptotic cell fraction while partially restoring HSP27 expression. Boldine suppressed HSP expression-most notably HSP27-and attenuated HSF1 phosphorylation under hyperthermia. In NCI-N87 cells, confirmatory experiments showed higher apoptosis after cotreatment, whereas hyperthermia did not further reduce viability or alter HSP levels.

CONCLUSIONS

Boldine enhances hyperthermia-induced apoptosis in AGS gastric cancer cells in association with attenuation of the HSF1-HSP stress response and ROS accumulation, supporting boldine as a potential thermosensitizing adjunct in gastric cancer therapy.