Monitoring of long-term effects of resveratrol on cell cycle progression of human HeLa cells after administration of a single dose.
Expression of the human papillomavirus-encoded oncoproteins E6 and E7 in human HeLa cervical carcinoma cells results in their escape from the proper control of the cell cycle progression. Therefore, their susceptibility to agents modulating cell cycle differs from that in cells in which the control of cell cycle regulation is intact. Recently, a number of experimental studies revealed that polyphenols, especially resveratrol, could exert a strong antiproliferative effect. Polyphenols (e.g., resveratrol or epicatechins), potent antioxidant agents, are abundant components of our diet and, therefore, may not only affect the proliferation of healthy cells in the organism but also modulate the action of distinct anticancer drugs. Indeed, it has been shown that resveratrol enhances the antimitotic effect exerted by roscovitine (ROSC), a potent cyclin-dependent kinase inhibitor, on human MCF-7 breast cancer cells. In the present contribution the action of resveratrol alone and in combination with ROSC on human HeLa cells was determined. Resveratrol inhibited proliferation of exponentially growing HeLa cells. Exposure of HeLa cells to 50 micromol/L resveratrol blocked cells in the S phase in a time-dependent manner. After 12 h the population of G(2)/M-phase cells completely disappeared, and during a further 12 h the frequency of S-phase cells markedly increased and reached approximately 90%. Thus, resveratrol synchronized HeLa cells in the S phase. After removal of resveratrol, synchronized HeLa cells rapidly progressed through the cell cycle. Four hours after medium change, more than 70% of cells moved into the G(2)/M phase. Moreover, resveratrol combined with ROSC enhanced the antiproliferative action of resveratrol.
Kramer
Matthias P
MP
Department of Medicine I, Institute of Cancer Research, Medical University Vienna, Vienna, Austria.
Wesierska-Gadek
Józefa
J
D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D002453:Cell Cycle / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects*; D002470:Cell Survival / Q000187:drug effects; D018844:Cyclin-Dependent Kinases / Q000037:antagonists & inhibitors; D004273:DNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D006367:HeLa Cells; D006801:Humans; D047428:Protein Kinase Inhibitors / Q000494:pharmacology; D011687:Purines / Q000494:pharmacology*; D000077185:Resveratrol; D012264:Ribonucleotide Reductases / Q000037:antagonists & inhibitors; D000077546:Roscovitine; D013267:Stilbenes / Q000494:pharmacology*; D013997:Time Factors
D000972:Antineoplastic Agents, Phytogenic; D004273:DNA, Neoplasm; D047428:Protein Kinase Inhibitors; D011687:Purines; D013267:Stilbenes; D000077546:Roscovitine; D012264:Ribonucleotide Reductases; D018844:Cyclin-Dependent Kinases; D000077185:Resveratrol