Biopolym. Cell. 2011; 27(2):124-131.
Structure and Function of Biopolymers
Signaling pathways involved in apoptosis induced by novel angucycline antibiotic landomycin E in Jurkat T leukemia cells
1Panchuk R. R.
- Institute of Cell Biology, NAS of Ukraine
14/16, Drahomanov Str., Lviv, Ukraine, 79005
Abstract
Aim. To study the molecular mechanisms of action of novel anticancer antibiotic landomycin E (LE). Methods. Annexin V/propidium iodide, DAPI (4',6-diamidino-2-phenylindole) staining, Western-blot analysis. Results. LE applied in 2 µg/ml dose (IC50), induced reactive oxygen species (ROS)-dependent splitting of poly [ADP-ribose] polymerase 1 (PARP-1) and DNA Fragmentation Factor 45 (DFF45) proteins involved in DNA reparation. This effect was observed 6 h after the start of treatment and it positively correlated with phosphatidyl serine externalization (early morphological marker of apoptosis). We suggest that cleavage of PARP-1 and DFF45 was mediated by active caspase-7 which is a key effector caspase in the LE-induced apoptosis in leukemia cells. We found that activation of initiator procaspase-10 (involved in receptor-mediated apoptosis) was the earliest detected event in LE-induced apoptotic signaling pathways; however, this activation was shown to be ROS-independent. We also demonstrated that the induction of apoptosis by LE is accompanied by activation of apoptosis-inducing factor (AIF) in mitochondria. Conclusions. Our data suggest that LE-induced cascade of apoptotic events is started by the initiator caspase-10 which leads to activation of the effector caspase-7 and AIF that is known to induce caspase-independent apoptosis involving ROS generation.
Keywords: tumor cells, landomyсin E, apoptosis, caspases, AIF, reactive oxygen species
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