title: Resveratrol induces growth inhibition, S-phase arrest, apoptosis, and changes in biomarker expression in several human cancer cell lines.
abstract: 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.
authors.affiliation: Herbert Irving Comprehensive Cancer Center, Department of Medicine, College of Physicians and Surgeons of Columbia University, New York, New York 10032, USA.
authors.forename: Andrew K
authors.initials: AK
authors.lastname: Joe
authors.forename: Hui
authors.initials: H
authors.lastname: Liu
authors.forename: Masumi
authors.initials: M
authors.lastname: Suzui
authors.forename: Muhammet E
authors.initials: ME
authors.lastname: Vural
authors.forename: Danhua
authors.initials: D
authors.lastname: Xiao
authors.forename: I Bernard
authors.initials: IB
authors.lastname: Weinstein
mesh_terms: 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
chemical_list: 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