Quercetin apoptosis inhibition

Colquhoun and Schumacher [98] have shown that y-linolcnic acid and eicosapentaenoic acid, which inhibit Walker tumor growth in vivo, decreased proliferation and apoptotic index in these cells. Development of apoptosis was characterized by the enhancement of the formation of reactive oxygen species and products of lipid peroxidation and was accompanied by a decrease in the activities of mitochondrial complexes I, III, and IV, and the release of cytochrome c and caspase 3-like activation of DNA fragmentation. Earlier, a similar apoptotic mechanism of antitumor activity has been shown for the flavonoid quercetin [99], Kamp et al. [100] suggested that the asbestos-induced apoptosis in alveolar epithelial cells was mediated by iron-derived oxygen species, although authors did not hypothesize about the nature of these species (hydroxyl radicals, hydrogen peroxide, or iron complexes ). 

Ferry DR, Smith A, Malkhandi J, F e DW, deTakats PG, Anderson D, Baker J, Kerr DJ (1996) Phase 1 clinical trial of the flavonoid quercetin pharmacokinetics and evidence for in vivo tyrosine kinase inhibition. Clin Cancer Res 2 659-668 Findik D, Song Q, Hidaka H, Lavin M (1995) Protein kinase A inhibitors enhance radiation-induced apoptosis. J Cell Biochem 57 12-21 Fine RL, Patel J, Chabner BA (1988) Phorbol esters induce multidrug resistance in human breast cancer cells. Proc Natl Acad Sci USA, 85 582-586 Finkenzeller G, Marme D, Hug H (1992) Inducible overexpression of human protein kinase C in NIH 3T3 fibroblasts results in growth abnormalities. Cell Signall 4 163-177... 

Perez-Vizcaino F, Bishop-Bailley D, Lodi F, Duarte J, Cogolludo A, Moreno L, Bosca L, Mitchell JA, Warner TD. 2006a. The flavonoid quercetin induces apoptosis and inhibits JNK activation in intimal vascular smooth muscle cells. Biochem Biophys Res Commun 346 919-925. 

At the same time, it has been reported recently that some flavonoids inhibit the synthesis of heat shock protein, which plays an important role in the protein metabolism and survival of cells. Quercetin, genistein and other flavonic agents induce apoptosis in different tumor cells through inhibition of heat shock protein and expression. Although these findings could suggest a possible anticancer therapy, it is necessary to learn much... 

Lee, L.T. et al.. Blockade of the epidermal growth factor receptor tyrosine kinase activity by quercetin and luteolin leads to growth inhibition and apoptosis of pancreatic tumor cells. Anticancer Res., 22, 1615,2002. 

Zhang, X., Xu, Q., and Saiki, L, Quercetin inhibits the invasion and mobility of murine melanoma B16-BL6 cells through inducing apoptosis via decreasing Bcl-2 expression, Clin. Exp. Metastasis, 18, 415, 2000. 

Suppressing mechanism This mechanism includes elimination of tumor cells, including growth inhibition by induction of cell-cycle arrest or apoptosis. Apigenin has been shown to induce G2/M arrest in SW480 and Caco-2 human colon carcinoma cells [40], Resveratrol and quercetin are reported to induce the expression of caspase-3 promoting apoptosis, arresting cells in G1 phase of the cell cycle, and decrease tiunor cell invasion [41]. 

EGCG and quercetin Human umbilical vein endothelial cells Inhibited endothelial apoptosis enhanced the expression of Bcl-2 protein and inhibited the expression of Bax protein and the cleavage and activation of caspase-3. [76] ... 

Quercetin and rutin increased the frequency of apoptotic cells in the male F344 rat model with chemically induced colon tumors [141]. Resveratrol enhanced upregulation of proapoptotic Smac/DIABLO protein and downregu-lated survivin in UVB exposure-mediated skin tumors [142]. Apigenin inhibits apoptosis of human prostate carcinoma tumor xenograft in athymic nude mice [143]. Caffeic acid phenethyl ester increased apoptosis and... 

Granado-Serrano AB, Martin MA, Bravo L et al (2006) Quercetin induces apoptosis via caspase activation, regulation of Bcl-2, and inhibition of PI-3-kinase/Akt and ERK pathways in a human hepatoma cell line (HepG2). J Nutr 136 2715-2721... 

In U-937 leukemia cells and mice harboring xenografts of this cell line, the proapoptotic effects of quercetin resulted in both the increased expression of the proapoptotic factor Bax and the inhibition of anti-apoptotic Mcl-l [291]. Quercetin causes apoptosis in both transformed and primary leukemia cells but not in normal blood peripheral mononuclear cells at concentrations up to 50 mM [292]. Further, quercetin has been shown to be a potent enhancer of TRAIL-induced apoptosis in prostate and hepatocellular carcinoma cells [293, 294]. 

---