Journal Article

Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells

Hélène Ferry-Dumazet, Olivier Garnier, Maria Mamani-Matsuda, Joseph Vercauteren, Francis Belloc, Christian Billiard, Maryse Dupouy, Denis Thiolat, Jean Pierre Kolb, Gerald Marit, Josy Reiffers and M.Djavad Mossalayi

in Carcinogenesis

Volume 23, issue 8, pages 1327-1333
Published in print August 2002 | ISSN: 0143-3334
Published online August 2002 | e-ISSN: 1460-2180 | DOI: http://dx.doi.org/10.1093/carcin/23.8.1327
Resveratrol inhibits the growth and induces the apoptosis of both normal and leukemic hematopoietic cells

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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.

Keywords: PBS, phosphate-buffered saline; ES, resveratrol

Journal Article.  5009 words.  Illustrated.

Subjects: Clinical Cytogenetics and Molecular Genetics

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