Figure 7. Mechanical stress-induced cell death in tumor spheroids acts via the mitochondrial pathway.

(A) Caspase-3 activity increases in monolayers of cancer cells in response to higher external stress. Cells were compressed for 17 hr. (B) Caspase-3 activity in spheroids made from two different cancer cell lines in response to different external stress (0 mmHg or 15 mmHg) and nutrient conditions (Normal: normal medium; Starvation: no glucose, no serum and 1% oxygen). (C) Typical caspase-3 activity (green) in spheroids (red) cultured in 3 of the conditions in B. Scale bar = 100 um. (D) Bcl-2 over-expression inhibits stress-induced apoptosis, but crmA transduction does not. Spheroids were compressed with 15 mmHg for 7 hr while being supplied with normal medium.