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

• Published in: Carcinogenesis (New York) Vol. 23; no. 8; pp. 1327 - 1333
• Main Authors: Ferry-Dumazet, Hélène, Garnier, Olivier, Mamani-Matsuda, Maria, Vercauteren, Joseph, Belloc, Francis, Billiard, Christian, Dupouy, Maryse, Thiolat, Denis, Kolb, Jean Pierre, Marit, Gerald, Reiffers, Josy, Mossalayi, M.Djavad
• Format: Journal Article
• Language: English
• Published: Oxford Oxford University Press 01-08-2002; Oxford Publishing Limited (England)
• Subjects: Antineoplastic agents; Apoptosis - drug effects; Biological and medical sciences; Bone Marrow Cells - cytology; Bone Marrow Cells - drug effects; Cell Division - drug effects; Chemotherapy; Humans; Leukemia - pathology; Medical sciences; PBS; Pharmacology. Drug treatments; phosphate-buffered saline; Resveratrol; Stilbenes - pharmacology; Antineoplastic agent; Human; Cell proliferation; Leukemia; Hematopoietic cell; Malignant hemopathy; In vitro; Biological activity; Stilbene derivatives; Signal transduction; Polyphenol; Cell death; Established cell line; Plant origin; Resveratrol; Tumor cell; Food; Apoptosis
• ISSN: 0143-3334; 1460-2180
• DOI: 10.1093/carcin/23.8.1327

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.