Viscum album agglutinin-I induces degradation of cytoskeletal proteins in leukaemia PLB-985 cells differentiated toward neutrophils: cleavage of non-muscle myosin heavy chain-IIA by caspases.
The role of the anti-cancer agent Viscum album agglutinin-I (VAA-I) in leukaemia PLB-985 cells differentiated toward a neutrophil-like phenotype by dimethylsulphoxide (PLB-985D) has never been studied. This study investigated whether or not VAA-I can induce cytoskeletal breakdown in PLB-985D cells, as previously observed in undifferentiated PLB-985 cells. VAA-I was found to induce apoptosis in PLB-985D cells, as assessed by cytology and by degradation of gelsolin, an event known to occur via caspase-3 activation. VAA-I induced cytoskeletal breakdown based on the disruption of the F-actin network and cleavage of paxillin, vimentin and lamin B(1). In addition, we demonstrated, for the first time, that non-muscle myosin heavy chain IIA (NMHC-IIA) was cleaved by VAA-I treatment. Degradation of NMHC-IIA was reversed by the pan caspase inhibitor z-VAD-fmk in PLB-985D cells and neutrophils. However, unlike lamin B(1), no NMHC-IIA was detected on the cell surface of apoptotic neutrophils. In conclusion, PLB-985D cells responded in a similar manner to neutrophils regarding the degradation of the tested cytoskeletal. Therefore, PLB-985D cells may provide a suitable substitute for neutrophils in screening experiments, preventing extensive neutrophil cell isolation.
INRS-Institut Armand-Frappier, Université du Québec, Pointe-Claire, QC, Canada.
Valérie
V
Lavastre
François
F
Binet
Eliane
E
Moisan
Sonia
S
Chiasson
Denis
D
Girard
D000970:Antineoplastic Agents / Q000627:therapeutic use*; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000235:genetics / Q000378:metabolism*; D002454:Cell Differentiation; D045744:Cell Line, Tumor; D003599:Cytoskeleton / Q000187:drug effects / Q000378:metabolism; D005434:Flow Cytometry; D006801:Humans; D034921:Lamin Type B / Q000032:analysis / Q000378:metabolism; D007938:Leukemia / Q000188:drug therapy* / Q000378:metabolism; D009504:Neutrophils / Q000276:immunology*; D024507:Nonmuscle Myosin Type IIA / Q000032:analysis / Q000378:metabolism*; D051419:Paxillin / Q000032:analysis / Q000378:metabolism; D028321:Plant Preparations / Q000627:therapeutic use*; D010940:Plant Proteins / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction; D054788:Ribosome Inactivating Proteins; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological / Q000627:therapeutic use*; D014746:Vimentin / Q000032:analysis / Q000378:metabolism
D000970:Antineoplastic Agents; D034921:Lamin Type B; D051419:Paxillin; D028321:Plant Preparations; D010940:Plant Proteins; D012333:RNA, Messenger; D054790:Ribosome Inactivating Proteins, Type 2; D014118:Toxins, Biological; C488865:VAA-I protein, Viscum album; D014746:Vimentin; D054788:Ribosome Inactivating Proteins; D020169:Caspases; D024507:Nonmuscle Myosin Type IIA