Quercetin-induced apoptosis in the monoblastoid cell line U937 in vitro and the regulation of heat shock proteins expression.
Quercetin, a widely distributed plant flavonoid, inhibits the growth of tumor cells and the expression of heat shock proteins. In this study, we examined quercetin-induced apoptosis of U937 cells in vitro and the regulation of heat shock proteins expression. The quercetin-induced apoptosis was demonstrated to be dose- and time-dependent. Flow cytometry analysis revealed that sub-G1 peak appeared at 12 hours, 24 hours and 48 hours respectively when treated with 50 mM of quercetin and at 6 hours, 12 hours, 24 hours and 48 hours with 100 mM of quercetin. Agarose gel electrophoresis demonstrated a typical ladder-like pattern of DNA fragments in the same time intervals with 50 mM of quercetin and at 6 hours only with 100 mM of quercetin. The distribution of DNA contents showed that U937 cells were accumulated mainly at G2/M phase when incubated with 50 mM of quercetin for 24 hours and 48 hours. There was no specific effect on cell cycle distribution at 100 mM of quercetin. On exposure to 100 mM of quercetin, the inhibition of hsp27 and hsp70 expression was observed from 12 hours to 48 hours and 6 hours to 48 hours respectively. The inhibition of hsp90 expression was not found eiyher at 50 mM or 100 mM of quercetin exposure. When incubated with 50 mM of quercetin, there was no inhibitory effect on hsp27, hsp70 and hsp90 expression by the Western blot analysis. These results suggested that it is dependent on the dose and exposure time of quercetin to induce apoptosis of U937 cells in vitro, to affect the cell cycle distribution and to regulate the expression of hsp27 and hsp70.
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Department of Experimental Surgery, Singapore General Hospital, Outram Road, Singapore 169608, Republic of Singapore. dosrongy@yahoo.com
Yang
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Zhang
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Mack
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D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects* / Q000502:physiology; D004247:DNA / Q000187:drug effects; D053938:DNA Fragmentation; D004305:Dose-Response Relationship, Drug; D004587:Electrophoresis, Agar Gel; D018840:HSP70 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D018841:HSP90 Heat-Shock Proteins / Q000187:drug effects / Q000378:metabolism; D006360:Heat-Shock Proteins / Q000187:drug effects* / Q000378:metabolism; D006801:Humans; D007399:Interphase; D047908:Intracellular Signaling Peptides and Proteins; D008938:Mitosis; D017346:Protein Serine-Threonine Kinases / Q000187:drug effects / Q000378:metabolism; D011794:Quercetin / Q000494:pharmacology*; D016196:S Phase; D013997:Time Factors; D020298:U937 Cells / Q000187:drug effects; D000099190:MAP-Kinase-Activated Kinase 2
D004247:DNA; D018840:HSP70 Heat-Shock Proteins; D018841:HSP90 Heat-Shock Proteins; D006360:Heat-Shock Proteins; D047908:Intracellular Signaling Peptides and Proteins; D017346:Protein Serine-Threonine Kinases; D011794:Quercetin; D000099190:MAP-Kinase-Activated Kinase 2