Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines.
OBJECTIVE
We examined the effects of the phytochemical resveratrol in six human cancer cell lines (MCF7, SW480, HCE7, Seg-1, Bic-1, and HL60).


RESULTS
Resveratrol induced marked growth inhibition in five of these cell lines, with IC(50) values of approximately 70-150 microM. However, only partial growth inhibition was seen in Bic-1 cells. After treatment with 300 microM resveratrol for 24 h, most of the cell lines were arrested in the S phase of the cell cycle. In addition, induction of apoptosis was demonstrated by the appearance of a sub-G(1) peak and confirmed using an annexin V-based assay. Cyclin B1 expression levels were decreased in all cell lines after 48 h of treatment. In SW480 cells, cyclin A, cyclin B1, and beta-catenin expression levels were decreased within 24 h. There was a decrease in cyclin D1 expression after only 2 h of treatment, and this persisted for up to 48 h. This decrease was partially blocked by concurrent treatment with the proteasome inhibitor calpain inhibitor I. Using a luciferase-based reporter assay, resveratrol did not inhibit cyclin D1 promoter activity in SW480 cells. Furthermore, using a reverse transcription-PCR-based assay, only a higher dose of resveratrol (300 microM) appeared to decrease cyclin D1 mRNA. Seg-1 cells expressed basal levels of cyclooxygenase-2 (cox-2), which was further induced by resveratrol. Neither basal levels nor induction of cox-2 was detectable in the remaining cell lines. Thus, cox-2 does not appear to be a critical target of this compound.


CONCLUSIONS
These studies provide support for the use of resveratrol in chemoprevention and cancer therapy trials. Cyclin D1, cyclin B1, beta-catenin, and apoptotic index could be useful biomarkers to evaluate treatment efficacy.
Joe
Andrew K
AK
Herbert Irving Comprehensive Cancer Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
Liu
Hui
H
Suzui
Masumi
M
Vural
Muhammet E
ME
Xiao
Danhua
D
Weinstein
I Bernard
IB
D016588:Anticarcinogenic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D014408:Biomarkers, Tumor / Q000378:metabolism*; D002453:Cell Cycle / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects*; D019938:Cyclin D1 / Q000235:genetics / Q000378:metabolism*; D016213:Cyclins / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D004305:Dose-Response Relationship, Drug; D005434:Flow Cytometry; D006801:Humans; D015151:Immunoblotting; D008156:Luciferases / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D012334:RNA, Neoplasm / Q000378:metabolism; D000077185:Resveratrol; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D016196:S Phase / Q000187:drug effects*; D013267:Stilbenes / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000187:drug effects* / Q000378:metabolism
D016588:Anticarcinogenic Agents; D014408:Biomarkers, Tumor; D016213:Cyclins; D017931:DNA Primers; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013267:Stilbenes; D019938:Cyclin D1; D008156:Luciferases; D012264:Ribonucleotide Reductases; D000077185:Resveratrol