Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells
We have compared the cytotoxic/cytostatic responses of the SKW6.4 lymphoblastoid B-cells to the alkylating agent chlorambucil, the purine analog fludarabine, the non-genotoxic activator of the p53 pathway, Nutlin-3, used alone or in association with the death-inducing ligand recombinant TRAIL. Expos...
| Main Authors: | , , , , , , , |
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| Format: | Journal Article |
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2008
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| Online Access: | http://hdl.handle.net/20.500.11937/3008 |
| _version_ | 1848744111373287424 |
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| author | Barbarotto, E. Corallini, F. Rimondi, E. Fadda, R. Mischiati, C. Grill, V. Vaccarezza, Mauro Celeghini, C. |
| author_facet | Barbarotto, E. Corallini, F. Rimondi, E. Fadda, R. Mischiati, C. Grill, V. Vaccarezza, Mauro Celeghini, C. |
| author_sort | Barbarotto, E. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | We have compared the cytotoxic/cytostatic responses of the SKW6.4 lymphoblastoid B-cells to the alkylating agent chlorambucil, the purine analog fludarabine, the non-genotoxic activator of the p53 pathway, Nutlin-3, used alone or in association with the death-inducing ligand recombinant TRAIL. Exposure to chlorambucil, fludarabine, and Nutlin-3 induced p53 accumulation and variably affected cell cycle progression in SKW6.4 lymphoblastoid cells. In particular, chlorambucil induced cell cycle accumulation at the G2/M checkpoint; Nutlin-3 induced early cell cycle arrest at the G1/S checkpoint, while fludarabine showed an intermediate behavior. On the other hand, recombinant TRAIL alone did not affect cell cycle progression but induced a rapid increase of apoptosis. Analysis of the gene expression profile of the p53-transcriptional targets showed distinct features between chlorambucil, Nutlin-3 and fludarabine, which likely account for their differential effect on cell cycle in SKW6.4 cells. In particular, chlorambucil upregulated the steady-state mRNA expression of SFN/14-3-3s, a gene involved in G2/M cell cycle arrest. Of note, all agonists upregulated TRAIL-R2 expression in SKW6.4 cells both at the mRNA and protein levels. Consistently, pretreatment with chlorambucil, fludarabine and Nutlin-3 enhanced SKW6.4 sensitivity to TRAIL-mediated apoptosis. © 2007 Wiley-Liss, Inc. |
| first_indexed | 2025-11-14T05:56:16Z |
| format | Journal Article |
| id | curtin-20.500.11937-3008 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| last_indexed | 2025-11-14T05:56:16Z |
| publishDate | 2008 |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-30082017-09-13T14:33:45Z Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells Barbarotto, E. Corallini, F. Rimondi, E. Fadda, R. Mischiati, C. Grill, V. Vaccarezza, Mauro Celeghini, C. We have compared the cytotoxic/cytostatic responses of the SKW6.4 lymphoblastoid B-cells to the alkylating agent chlorambucil, the purine analog fludarabine, the non-genotoxic activator of the p53 pathway, Nutlin-3, used alone or in association with the death-inducing ligand recombinant TRAIL. Exposure to chlorambucil, fludarabine, and Nutlin-3 induced p53 accumulation and variably affected cell cycle progression in SKW6.4 lymphoblastoid cells. In particular, chlorambucil induced cell cycle accumulation at the G2/M checkpoint; Nutlin-3 induced early cell cycle arrest at the G1/S checkpoint, while fludarabine showed an intermediate behavior. On the other hand, recombinant TRAIL alone did not affect cell cycle progression but induced a rapid increase of apoptosis. Analysis of the gene expression profile of the p53-transcriptional targets showed distinct features between chlorambucil, Nutlin-3 and fludarabine, which likely account for their differential effect on cell cycle in SKW6.4 cells. In particular, chlorambucil upregulated the steady-state mRNA expression of SFN/14-3-3s, a gene involved in G2/M cell cycle arrest. Of note, all agonists upregulated TRAIL-R2 expression in SKW6.4 cells both at the mRNA and protein levels. Consistently, pretreatment with chlorambucil, fludarabine and Nutlin-3 enhanced SKW6.4 sensitivity to TRAIL-mediated apoptosis. © 2007 Wiley-Liss, Inc. 2008 Journal Article http://hdl.handle.net/20.500.11937/3008 10.1002/jcb.21649 restricted |
| spellingShingle | Barbarotto, E. Corallini, F. Rimondi, E. Fadda, R. Mischiati, C. Grill, V. Vaccarezza, Mauro Celeghini, C. Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title | Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title_full | Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title_fullStr | Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title_full_unstemmed | Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title_short | Differential effects of chemotherapeutic drugs versus the MDM-2 antagonist Nutlin-3 on cell cycle progression and induction of apoptosis in SKW6.4 lymphoblastoid B-cells |
| title_sort | differential effects of chemotherapeutic drugs versus the mdm-2 antagonist nutlin-3 on cell cycle progression and induction of apoptosis in skw6.4 lymphoblastoid b-cells |
| url | http://hdl.handle.net/20.500.11937/3008 |