Carcinogenesis, Vol. 23, No. 8, 1327-1333,
August 2002
© 2002 Oxford University Press
MOLECULAR EPIDEMIOLOGY AND CANCER PREVENTION |
Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells
Bone Marrow Transplantation and Hematology Laboratories, CNRS UMR5540, EA 482 and GESNIT-EA 491, Victor Segalen Bordeaux-2 University, Bordeaux, France and
1 Curie Institute, INSERM U366, 75005 Paris, France
It is often postulated that trans-3,4’,5-trihydroxystilbene (resveratrol, RES) exhibits cell growth regulatory and chemopreventive activities. However, mechanisms by which this polyphenol inhibits tumor cell growth, and its therapeutic potential are poorly understood. Using various human leukemia cells, we have first defined the anti-tumoral doses of this compound. RES inhibited the proliferation and induced the apoptosis of all tested lymphoid and myeloid leukemia cells with IC50 = 5–43 µM. Prior to apoptosis, RES-induced caspase activity in a dose-dependent manner and cell cycle arrest in G2/M-phase, correlating with a significant accumulation of cyclins A and B. Leukemia cell death with RES required both caspase-dependent and -independent proteases, as it was significantly inhibited by simultaneous addition of Z-VAD-FMK and leupeptin to these cultures. While RES did not affect non-activated normal lymphocytes, this agent decreased the growth and induced the apoptosis of cycling normal human peripheral blood lymphocytes at lower concentrations (IC50 <8 µM) than those required for most leukemia cells. RES also induced the apoptosis of early normal human CD34+ cells and decreased the number of colonies generated by these precursor cells in a dose-dependent manner (IC50 = 60 µM). Together, the data point to the complexity of RES-mediated signaling pathways and revealed the high anti-proliferative and proapoptotic activities of RES in normal cycling hemopoietic cells.
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