PAC-1 activates procaspase-3 by chelating zinc ions, thus relieving the zinc-mediated inhibition and allowing procaspase-3 to auto-activate itself to caspase-3.PAC-1 can not induce cell death and caspase-3 activation in Apaf-1 knockout cells, suggesting that apoptosome formation is essential for caspase-3 activation by PAC-1-mediated cell death.
In vivo
Oral administration of PAC-1 (50 or 100 mg/kg) significantly retards tumor growth of NCI-H226 lung cancer xenograft in a dose-dependent manner, and markedly prevents the cancer cells from infiltrating the lung tissue.