Abstract
Resveratrol (3,5,4′-trihydroxy-trans-stilbene), in the concentration range of 20 μM and above, induced arrest in the S-phase and apoptosis in the T cell-derived T-ALL lymphocytic leukemia cell line CEM-C7H2 which is deficient in functional p53 and p16. Expression of transgenic p16/INK4A, which causes arrest in G0/G1, markedly reduced the percentage of apoptotic cells. Antagonist antibodies to Fas or FasL, or constitutive expression of crmA did not diminish the extent of resveratrol-induced apoptosis. Furthermore, a caspase-8-negative, Fas-resistant Jurkat cell line was sensitive to resveratrol-induced apoptosis which could be strongly inhibited in the Jurkat as well as in the CEM cell line by z-VAD-fmk and z-IETD-fmk. The almost complete inhibition by z-IETD-fmk and the lack of inhibition by crmA suggested caspase-6 to be the essential initiator caspase. Western blots revealed the massive conversion of procaspase-6 to its active form, while caspase-3 and caspase-2 were proteolytically activated to a much lesser extent. Cell Death and Differentiation (2000) 7, 834–842
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Abbreviations
- Fas:
-
APO-1/CD95
- FasL:
-
Fas ligand
- rsFasL:
-
recombinant soluble FasL
- FACS:
-
fluorescence activated cell sorter
- FITC:
-
fluorescein isothiocyanate
- PBS:
-
phosphate buffered saline
- TBS:
-
TRIS buffered saline
- SDS:
-
sodium dodecyl sulfate
- crmA:
-
cytokine response modifier A
- TNFα:
-
tumor necrosis factor α
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Acknowledgements
This work was supported by grants from the Austrian Science Fund (SFB-F204), the Österreichische Krebshilfe-Krebsgesellschaft Tirol and the Province of Tyrol. We are indebted to Ms. Rajam Csordas-Iyer for critical reading and editorial assistance.
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Bernhard, D., Tinhofer, I., Tonko, M. et al. Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells. Cell Death Differ 7, 834–842 (2000). https://doi.org/10.1038/sj.cdd.4400719
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DOI: https://doi.org/10.1038/sj.cdd.4400719
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