PTEN and lung cancer: Collectively, these findings suggest a hierarchy model of hirsutine-induced apoptosis in human lung cancer cells in which hirsutine-induced ROCK1 activation represents a primary event resulting in PTEN activation and PI3K/Akt inactivation, in turn, leading to GSK3β dephosphorylation and mPTP opening, and culminating in caspase-3 activation and apoptosis (Fig. 8).