Resveratrol selectively inhibits leukemia cells: a prospective agent for ex vivo bone marrow purging.
Ex vivo purging of contaminating tumor cells may reduce the incidence of relapse in patients undergoing bone marrow transplantation. In this study we demonstrate that resveratrol, a phytoalexin with anti-oxidant and chemopreventive activity, exhibits anti-leukemic activity against mouse (32Dp210, L1210) and human (U937, HL-60) leukemic cell lines by inhibiting cell proliferation. Long-term exposure to resveratrol also inhibits the clonal growth of normal hematopoietic progenitor cells but at a higher IC50 of resveratrol than that for most of the leukemia cell lines tested. The inhibitory effect of resveratrol on hematopoietic progenitors is partially reversible, whereas the effect on leukemia cells is largely irreversible. The inhibition of leukemia cells by resveratrol involves nucleosomal DNA fragmentation (apoptosis). On the other hand, resveratrol does not induce or enhance spontaneously occurring apoptotic death in normal hematopoietic progenitor cells. In vivo experiments performed with untreated and resveratrol-treated bone marrow showed comparable hematopoietic reconstitution in lethally irradiated mice (10 Gy) as determined by survival, hematologic recovery, and the number of hematopoietic progenitor cells present in the marrow of reconstituted animals. Taken together, these results indicate the potential use of resveratrol for ex vivo pharmacological purging of leukemia cells from bone marrow autografts without significant loss in the hematopoietic activity of progenitor cells.
Gautam
S C
SC
Division of Hematology/Oncology, Department of Medicine, Henry Ford Health System, Detroit, MI 48202, USA.
Xu
Y X
YX
Dumaguin
M
M
Janakiraman
N
N
Chapman
R A
RA
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D016465:Bone Marrow Purging; D016026:Bone Marrow Transplantation; D002455:Cell Division / Q000187:drug effects; D053938:DNA Fragmentation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D006085:Graft Survival / Q000187:drug effects; D018922:HL-60 Cells / Q000187:drug effects; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D000077185:Resveratrol; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects; D020298:U937 Cells / Q000187:drug effects; D014916:Whole-Body Irradiation
D000972:Antineoplastic Agents, Phytogenic; D013267:Stilbenes; D000077185:Resveratrol