Nanomolar level of resveratrol (trans-3,5,4'-trihydroxystilbene) is required, but is not sufficient, to inhibit the growth of human monocytoid tumor cells through an apoptotic-like mechanism.
The chemopreventive activity of resveratrol, a stilbene found in grapes and wine, was evaluated in a human monocytic leukemia cell line at the same concentration (100 nM to 1 microM) as that found in the blood-stream after moderate wine intake. As early as at 4 h after intake, resveratrol exhibited antiproliferative and cytotoxic activity. At the same time, some apoptotic-like phenomena were detected such as cell membrane perturbation (phosphatidylserine-annexin V binding), apolipoprotein (APO)-1/FAS (CD95) expression and mitochondrial (delta psi) depolarization. The anticancer drug camptothecin, used as a positive control, did not significantly increase APO-1/FAS (CD95) levels, while only a modest increase in APO-1/FAS-CD95 ligand (CD95-L) was detected. At 12 h, however, resveratrol at concentrations of 100 nM and 1 microM did not exhibit the same antiproliferative activity and increased cell proliferation was correlated to a significant increase in FAS-L expression. We conclude that treatment with low doses of resveratrol, such as those found after moderate wine intake, is not sufficient to stop human leukemia cell line proliferation and that cell resistance, marked by high FAS-L (CD95-L) expression, could be mediated by low (delta psi) mitochondria-released antiapoptotic factors such as BCL-2. It is also suggested that the synergistic action of other wine components with resveratrol might, at least partially, explain its chemopreventive activity.
Corsi
M M
MM
Clinical Pathology Laboratory, Institute of General Pathology, Faculty of Medicine, University of Milan, Milan, Italy. mmcorsi@unimi.it
Ponti
W
W
Ferrara
F
F
Venditti
A
A
Malavazos
A
A
Ruscica
M
M
Mihali
D
D
Diana
G M
GM
Paraboni
L
L
Bertelli
A A E
AA
D016588:Anticarcinogenic Agents / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D002455:Cell Division / Q000187:drug effects; D003864:Depression, Chemical; D004305:Dose-Response Relationship, Drug; D053222:Fas Ligand Protein; D005455:Fluorescent Antibody Technique; D006801:Humans; D008562:Membrane Glycoproteins / Q000378:metabolism; D008564:Membrane Potentials; D008928:Mitochondria / Q000187:drug effects / Q000502:physiology; D009000:Monocytes / Q000166:cytology / Q000187:drug effects; D000077185:Resveratrol; D013267:Stilbenes / Q000008:administration & dosage / Q000494:pharmacology*; D020298:U937 Cells; D019014:fas Receptor / Q000378:metabolism
D016588:Anticarcinogenic Agents; C505661:FASLG protein, human; D053222:Fas Ligand Protein; D008562:Membrane Glycoproteins; D013267:Stilbenes; D019014:fas Receptor; D000077185:Resveratrol