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| Titel: |
Signaling pathways involved in apoptosis induced by novel angucycline antibiotic landomycin E in Jurkat T leukemia cells |
| Auteur: |
Panchuk R. R. |
| Verschenen in: |
Biopolymers and cell |
| Paginering: | Jaargang 27 (2011) nr. 2 pagina's 124-131 |
| Jaar: |
2011 |
| Inhoud: |
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. |
| Uitgever: |
Institute of molecular biology and genetics, National Academy of Sciences of Ukraine (provided by DOAJ) |
| Bronbestand: |
Elektronische Wetenschappelijke Tijdschriften |
Details van artikel 6 van 11 gevonden artikelen
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