Exp Mol Med.  2003 Dec;35(6):467-474.

Resveratrol derivatives potently induce apoptosis in human promyelocytic leukemia cells

Affiliations
  • 1Department of Physiology, School of Medicine, Kyungpook National University Daegu 700-422, Korea. wjleek@knu.ac.kr
  • 2Department of Food Science and Nutrition, Catholic University of Daegu, Hayang, Gyeongbuk 712-702, Korea.

Abstract

Resveratrol has been shown to possess antioxidant and anticancer activities, but little is known on the effect of resveratrol derivatives. Recently we have isolated resveratrol and its dimers and trimers from peony (Paeonia lactiflora) seeds, and reported their strong antioxidant and cytotoxic activity. In the present study, we have evaluated cellular effects of resveratrol derivatives; viniferin, gnetin H, and suffruticosol B on the proliferation and apoptosis in HL-60 cells in vitro. All resveratrol and its derivatives reduced viability of HL-60 cells in a dose-dependent manner with their IC(50)values of 20-90 micrometer. Ascending orders of IC(50)values were suffruticosol B, gnetin H, viniferin and resveratrol respectively. HL-60 cells treated with the four stilbenes exhibited the distinct morphological changes characteristics of cell apoptosis such as chromatin condensation, apoptotic bodies, and DNA fragmentations. A time-dependent histogram of the cellular DNA analyzed by flow cytometry revealed a rapid increase in subdiploid cells and a concomitant decrease in diploid cells exposed to 100 micrometer resveratrol for 0-24 h. Cells treated with 25 micrometer of resveratrol, viniferin, gnetin H, and suffruticosol B for 24 h resulted in increment of sub-G1 population by 51, 5, 11 and 59%, respectively. Treatment of cells with 0-20 micrometer resveratrol for 5 h produced a concentration-dependent decrease in cytochrome P450 (CYP) 1B1 mRNA levels. Suffruticosol B also suppressed CYP1B1 gene expression. These results demonstrated that resveratrol oligomers also strongly suppressed HL-60 cell proliferation, and induced DNA damage. In addition, CYP1B1 gene supression may suggest an involvement in the resveratrol-induced apoptosis in HL-60 cells.

Keyword

antioxidants; apoptosis; cell death; neoplasm; paeonia

MeSH Terms

Apoptosis/*drug effects
Cell Cycle/drug effects
Cytochrome P-450 Enzyme System/genetics
Flow Cytometry
Gene Expression Regulation, Neoplastic/drug effects
HL-60 Cells
Humans
Leukemia/genetics/*pathology
RNA, Messenger/genetics/metabolism
Stilbenes/*chemistry/*pharmacology/toxicity
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