[99mtc]tc-sestamibi bioaccumulation can induce apoptosis in breast cancer cells: Molecular and clinical perspectives

The aim of this study was to investigate the possible role of [99mTc]Tc-Sestamibi in the regulation of cancer cell proliferation and apoptosis. To this end, the in vivo values of [99mTc]Tc-Sestamibi uptake have been associated with the in-situ expression of both Ki67 and caspase-3. For in vitro investigations, BT-474 cells were incubated with three different concentrations of [99mTc]Tc-Sestamibi: 10 mu g/mL, 1 mu g/mL, and 0.1 mu g/mL. Expression of caspase-3 and Ki67, as well as the ultrastructure of cancer cells, was evaluated at T0 and after 24, 48, 72, and 120 h after [99mTc]Tc-Sestamibi incubation. Ex vivo data strengthened the known association between sestamibi uptake and Ki67 expression. Linear regression analysis showed a significant association between sestamibi uptake and the number of apoptotic cells evaluated as caspase-3-positive breast cancer cells. As concerning the in vitro data, a significant decrease of the proliferation index was observed in breast cancer cells incubated with a high concentration of [99mTc]Tc-Sestamibi (10 mu g/mL). Amazingly, a significant increase in caspase-3-positive cells in cultures incubated with 10 mu g/mL [99mTc]Tc-Sestamibi was observed. This study suggested the possible role of sestamibi in the regulation of pathophysiological processes involved in breast cancer.