We recently demonstrated that
TLCK and
TPCK could act as potent but nonspecific inhibitors of mature
caspases [Frydrych and Mlejnek [2008] J Cell Biochem 103:1646-1656]. The question whether
TLCK and
TPCK inhibit simultaneously
caspase activation and/or processing remained, however, open. In this article, we demonstrated that
TPCK even enhanced
caspase-3 and
caspase-7 processing although it substantially inhibited
caspase-3 and
caspase-7 enzymatic (
DEVDase) activity in HL-60 cells exposed to various cell death inducing stimuli. Under the same conditions,
TLCK had no effect or affected
caspase-3 and
caspase-7 processing marginally depending on cell treatment used. Importantly,
TLCK substantially inhibited
caspase-3 and
caspase-7 enzymatic (
DEVDase) activity irrespectively to the treatment used. Interestingly, treatment of cells with toxic concentrations of
TPCK alone was accompanied by full
caspase-3 and -7 processing even if it induced
necrosis. In contrast, treatment of cells with concentrations of
TLCK that caused
necrosis was accompanied by only partial
caspase-3 and
caspase-7 processing. Our results clearly indicated that
TPCK and
TLCK did not inhibit
caspase-3 and -7 enzymatic activity by prevention of their activation and/or processing.