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Resveratrol causes arrest in the S-phase prior to Fas-independent apoptosis in CEM-C7H2 acute leukemia cells

2000; Springer Nature; Volume: 7; Issue: 9 Linguagem: Inglês

10.1038/sj.cdd.4400719

1476-5403

David Bernhard, Ingeborg Tinhofer, Martin Tonko, H. Hubl, Michael J. Ausserlechner, Richard Greil, Reinhard Kofler, Adam Csordás,

RNA Interference and Gene Delivery

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