Induction of apoptosis and NF-$\kappa$B by quercetin in growing murine L1210 lymphocytic leukaemic cells potentiated by TNF-$\alpha$

Abstract

-Polyphenol quercetin induced apoptosis in proliferating murine L1210 lymphocytic cells. DNA damage, as well as apoptosis and withdrawal from the cell cycle were transient. The above mentioned death promoting activity of quercetin was enhanced by physiological concentrations of TNF-α. At the same time, indices of cell viability dropped. However, the extent and tendency of the initially enhanced cell mortality steadily diminished throughout the experiment. After 12 h the G2/M phase reappeared. After 24 h all indices almost returned to control levels indicating either the selection of subpopulation of unaffected leukaemic cells or cells developing resistance to the treatment. A DNA ladder of oligonucleosomes was observed for apoptogenic treatments. We conclude that quercetin unmasked cell death, promoting the activity of TNF-α. However, after 12 and 24 h of exposure, surviving cells could complete the cell cycle and finally recover. At the same time, increased NF-κB activation was demonstrated by immunoblotting of the immunoreactive RelA/p65 subunit in nuclear extracts. Exposure to TNF-α or quercetin was crucial for increased activity of NF-κB, which may implicate an increasing resistance to their cytotoxicity. quercetin / TNF-α / leukaemia / apoptosis / NF-κB Reprod. Nutr. Dev. 40 (2000) 441

Dietary polyphenol quercetin targets pancreatic cancer stem cells

“…This assumption is reinforced by our experiments in which we observed minimal toxicity in primary human fibroblasts and mesenchymal stromal/stem cells upon incubation with quercetin and sulforaphane (11). Our data are consistent with the findings of Orzechowski et al (27) who demonstrated quercetin-induced enhanced binding of p65/cRel containing NF-κB dimers in nuclear extracts of murine lymphocytic leukemia cells. Conversely, other authors show inhibition of NF-κB binding activity in response to quercetin (19,28).…”

INHIBITION OF LUNG CANCER CELL GROWTH BY QUERCETIN GLUCURONIDES VIA G2/M ARREST AND INDUCTION OF APOPTOSIS

“…Moreover, quercetin-mediated apoptosis may be related to many factors such as stress proteins, disruption of microtubules, nuclear factor B, Cox-2, p53, survivin, c-Jun NH 2 -terminal kinase, mitogenactivated protein kinase kinase-extracellular signal-regulated kinase, Bcl-2 family proteins, heat shock proteins, DNA topoisomerase II, release of cytochrome c, and activation of caspases (Yoshida et al, 1990;Orzechowski et al, 2000;Choi et al, 2001;Jakubowicz-Gil et al, 2002;Kaneuchi et al, 2003;Cheong et al, 2004;Kuo et al, 2004;Nguyen et al, 2004;Ong et al, 2004). Quercetin has been reported to inhibit the growth of various human cancers, including leukemia, breast, esophagus, colon, prostate, nasopharyngeal, endometrial, and lung cancers (Yoshida et al, 1990;Orzechowski et al, 2000;Choi et al, 2001;Jakubowicz-Gil et al, 2002;Kaneuchi et al, 2003;Cheong et al, 2004;Kuo et al, 2004;Nguyen et al, 2004;Ong et al, 2004). It is imperative to investigate the biological effects of quercetin glucuronides that are more close to the in vivo situation.…”

Bioactive substances of plant origin in food - impact on genomics

“…Sato et al [87] or Ishikawa et al [43] reported the suppression of NF-kB activation by quercetin in human synovial cells, or glomerular cells, respectively, but the cells were studied in serum free medium, with additional one day fasting as the pretreatment period to induce cell quiescence. We reported transient activation of this transcription factor by quercetin in conditions favoring cell proliferation [77]. It therefore appears, that quercetin-induced NF-kB activation is characterized by cell specificity.…”

“…On the contrary, flavonoids are cytopathic to tumor cells. The puzzling issue of the developing resistance of tumor cells to cytopathic actions of flavonols in the presence of TNF-a-stimulated NF-kB activity remains unexplained and ambiguous [77].…”