Distinct mechanisms of DNA damage in apoptosis induced by quercetin and luteolin

Abstract

Quercetin has been reported to have carcinogenic effects. However, both quercetin and luteolin have anti-cancer activity. To clarify the mechanism underlying the carcinogenic effects of quercetin, we compared DNA damage occurring during apoptosis induced by quercetin with that occuring during apoptosis induced by luteolin. Both quercetin and luteolin similarly induced DNA cleavage with subsequent DNA ladder formation, characteristics of apoptosis, in HL-60 cells. In HP 100 cells, an H2O2-resistant clone of HL-60 cells, the extent of DNA cleavage and DNA ladder formation induced by quercetin was less than that in HL-60 cells, whereas differences between the two cell types were minimal after treatment with luteolin. In addition, quercetin increased the formation of 8-oxo-7,8-dihydro-2'-deoxyguanosine (8-oxodG), an indicator of oxidative DNA damage, in HL-60 cells but not in HP 100 cells. Luteolin did not increase 8-oxodG formation, but inhibited topoisomerase II (topo II) activity of nuclear extract more strongly than quercetin and cleaved DNA by forming a luteolin-topo II-DNA ternary complex. These results suggest that quercetin induces H2O2-mediated DNA damage, resulting in apoptosis or mutations, whereas luteolin induces apoptosis via topo II-mediated DNA cleavage. The H2O2-mediated DNA damage may be related to the carcinogenic effects of quercetin.

trans-Resveratrol induces apoptosis in human breast cancer cells MCF-7 by the activation of MAP kinases pathways

“…The involvement of ROS has been proposed as upstream event occurring during treatment with high (micro-molar) concentrations of trans-resveratrol [1,21], as well as with other polyphenols, including epigallocatechin-3-gallate [44,53), woodfordin I [35] and quercetin [33,64]. In our experimental system ROS burst occurs precociously (within the first hour) and the detrimental effects produced were confirmed by the increase in lipid peroxidation by-products, MDA and 4-HNE.…”

MAPK signaling in neurodegeneration: influences of flavonoids and of nitric oxide

“…However, the actions of flavonoids are complex and often seemingly antagonistic or paradoxical. For example, while flavonoids are described as antioxidant agents protecting against oxidative insults to cells and apoptosis [11,13,88], others have found flavonoids to be pro-oxidants and -apoptotic [33,212,221]. Thus, it becomes clear that the effects of flavonoids depend on different factors such as the specific compound used, the cell type, concentrations, experimental design, and the general context in which flavonoids are used.…”

Quercetin-Induced PC12 Cell Death Accompanied by Caspase-Mediated DNA Fragmentation

“…Several studies have shown that quercetin is a pro-oxidant and cytotoxic in leukemic cells. 7,8) Flavonoids including quercetin caused apoptosis in carcinoma/cancer cells 2,9) and showed cytotoxicity in normal cells including human umbilical vein endothelial cells.…”

“…Several studies have shown that quercetin is a pro-oxidant and cytotoxic in leukemic cells. 7,8) Flavonoids including quercetin caused apoptosis in carcinoma/cancer cells 2,9) and showed cytotoxicity in normal cells including human umbilical vein endothelial cells.10) The neuronal density of the hippocampus in gerbils subjected to infusion of quercetin to the ventricle was significantly lower than that in control.11) Thus, the effects of quercetin on cell death and/or apoptosis in cells including neuronal cells have not been well confirmed.The PC12 cell line, a rat adrenal medullary pheochromocytoma, is a useful model for studying the survival of neuronal cells. Native PC12 cells divide and resemble precursors of adrenal chromaffin cells and sympathetic neurons when grown in the presence of serum, and gradually attain the phenotypic properties of sympathetic neurons on the addition of nerve growth factor (NGF).…”

“…Several studies have shown that quercetin is a pro-oxidant and cytotoxic in leukemic cells. 7,8) Flavonoids including quercetin caused apoptosis in carcinoma/cancer cells 2,9) and showed cytotoxicity in normal cells including human umbilical vein endothelial cells. 10) The neuronal density of the hippocampus in gerbils subjected to infusion of quercetin to the ventricle was significantly lower than that in control.…”