Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Matsuo, Mitsuyoshi; Sasaki, Naoki; Saga, Kotaro; Kaneko, Takao

doi:10.1248/bpb.28.253

Cited by 212 publications

(173 citation statements)

References 37 publications

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“…Under our conditions, rutin did not show quercetin-like toxic effect in PC12 cells, as previously reported in human promyeloleukemic HL-60 cells 27) and endothelial cells. 10) Some reports showed that rutin could not show quercetin-like effect on undifferentiated and differentiated PC12 cells. 28,29) However, both rutin and quercetin showed similar effect, 20,30) and quercetin-3-o-galactoside showed protective effects against cytotoxicity induced by oxidative stress in PC12 cells.…”

Section: Discussionmentioning

confidence: 99%

“…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.…”

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confidence: 89%

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

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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Flavonoids, a large group of polyphenolic compounds found in fruits and vegetables, have attracted much attention because of their broad pharmacological, particularly antioxidative, activities.1,2) Flavonoids may exert beneficial effects on a number of disease states including cancer, cardiovascular disease, inflammation and neurodegenerative disorders. 1,2)The pathology of neurodegenerative disorders including Alzheimer's disease and aging is associated with oxidative stress caused by reactive oxygen species and reactive nitrogen species.2,3) If oxidative stress is suppressed by compounds in foods, such as flavonoids, this may act as a preventive measure to reduce damage and/or disfunction of cells. Quercetin (3,3Ј,4Ј,5,, which possesses a wide spectrum of pharmacological and biological properties, 2,4) is found in many kinds of food. The daily Western diet contains on average about 25 mg of various flavonoids, of which quercetin is a major ingredient (16 mg/d).5) Quercetin can scavenge free radicals directly and inhibit the oxidation of various molecules resulting in the activation of antioxidant defense pathways in vivo and in vitro. However, the actions of flavonoids are complex and paradoxical in some cases. 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). Previously, we reported that the treatment of native and undifferentiated PC12 cells with an inhibitor of thioredoxin reductase and dopaminergic neurotoxins such as 1-methyl-4-phenylpyridinium ion (MPP ϩ ) caused apoptosis via a caspase-mediated pathway. 12,13) Quercetin has been shown to inhibit cell death and/or apoptosis induced by various stimuli including oxidative stress and MPP ϩ in differentiated PC12 cells. [14][15][16] In undifferentiated PC12 cells, however, antioxidants including quercetin did not have a protective effect against cell death induced by oxidative stress including MPP ϩ . 15,16) The effect of quercetin on cell survival and death in undifferentiated PC12 cells has not been well established. In the present study, we investigated whether quercetin causes cell death in undifferentiated PC12 cells or not. The effect of genistein, a soy isoflavone that has the pro-apoptotic ac...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 89%

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

Sasaki

Nakamura

Tsuchiya

et al. 2007

Biological & Pharmaceutical Bulletin

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“…After the treatment, the cells were washed and treated either with a 10 % MTT solution or with a 1 % neutral red solution to determine cell survival (13,14). The absorbance of formazan (540 nm) or neutral red (492 nm) imported into cellular lysosome was measured using a microtitre reader (Cecil Instruments Ltd., Technical Centre Cambridge, UK) and compared with the absorbance measured in untreated (control) cells.…”

Section: Cell Survivalmentioning

confidence: 99%

“…Cell survival was calculated relative to control. The experiments were repeated three times (13,14).…”

Section: Cell Survivalmentioning

confidence: 99%

Cytotoxic and Genotoxic Effects of the Quercetin/Lanthanum Complex on Human Cervical Carcinoma Cells In Vitro

Durgo

Halec

Šola

et al. 2011

Archives of Industrial Hygiene and Toxicology

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Quercetin is the main fl avonoid in diet with a potential in the treatment of cancer, cardiovascular, and neurodegenerative diseases. Due to its specifi c planar chemical structure, quercetin readily forms chelates with metal ions. Complexes of bioactive compounds and metal ions such as lanthanum often show strong cytotoxic and antitumour properties. The aim of this study was to compare the genotoxic effects of the quercetin/lanthanum complex on human cervical carcinoma cells with compare it to the effects of free ligands, quercetin, and lanthanum alone. The quercetin/lanthanum complex showed considerable cytotoxicity in the concentration range of (100 to 1000) mmol mL -1 and exposure time of three hours. The complex also induced a dose-dependent pro-oxidative effects and the formation of single-strand and double-strand DNA breaks. Although we obtained promising results on the cell level, future experiments should answer whether the quercetin/lanthanum complex is cancer-specific and stable enough in physiological conditions to make a potential new antitumour drug. Arh Hig Rada Toksikol 2011;62:221-227 Evidence abounds about antitumour activity of small-molecule compounds, including metal complexes with fl avonoids, which directly interact with DNA (1). Recently, much attention has also been paid to how cancer cell growth and apoptosis are affected by rare earth metals and compounds such as lanthanum and cerium salts (2, 3). KEY WORDS: chelates, DNA damage, fl avonoid/metal complexes, oxidative damage Durgo K et al. QUERCETIN/LANTHANUM COMPLEX EFFECTS ON HUMAN CERVICAL CARCINOMA CELLSLanthanum salts can arrest the cell cycle in the G1/S phase in leukemic cell lines (2) and inhibit telomerase activity in the lymphoblastoid tumour cell line (3). Both induce apoptotic events. Contrary to this effect observed in tumour cells, no effect could be determined in normal bone marrow haematopoietic cells (2). Lanthanum complexed with bioactive compounds from plants has shown even stronger cytotoxic effect than when administered alone (4), suggesting that electron transfer and oxidative stress are responsible for the cytotoxic effect. Kostova et al. (5) found that lanthanum complexes with biscoumarins caused apoptotic cell death of several leukaemia and lymphoma cell lines, causing DNA fragmentation and morphological changes. The authors believe that this cytotoxic effect depends on the metal-ligand structure. Wang et al. (1) analysed a lanthanum-naringenin Schiff-base complex and found that the ligands were coordinated to the lanthanum ion through deprotonated hydroxyl groups. This complex bound directly to calf-thymus DNA, probably through intercalation, while the same concentrations caused a strong cytotoxic effect on human leukaemia and lung adenocarcinoma cells. Intercalation is the main cytotoxic mechanism of numerous antitumour agents such as cisplatin, but their use is limited by drug resistance. Determination and synthesis of new agents

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“…In the latter case, 0.02x corresponds to a concentration 50 times lower than the original extract concentration. After 48 and 72 hours (period of early and late exponential phase), DMEM was removed, and cells incubated with a 10 % MTT solution (15,16). Viable cells have active mitochondrial dehydrogenase enzymes which metabolise yellow-coloured tetrazolium salt into a blue formazan.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In Vitro

Durgo

Kostić

Gradiški

et al. 2011

Archives of Industrial Hygiene and Toxicology

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Green tea (Camellia sinensis) contains several bioactive compounds which protect the cell and prevent tumour development. Phytochemicals in green tea extract (mostly fl avonoids) scavenge free radicals, but also induce pro-oxidative reactions in the cell. In this study, we evaluated the potential cytotoxic and prooxidative effects of green tea extract and its two main fl avonoid constituents epigallocatechin gallate (EGCG) and epicatechin gallate (ECG) on human laryngeal carcinoma cell line (HEp2) and its crossresistant cell line CK2. The aim was to see if the extract and its two fl avonoids could increase the sensitivity of the cisplatin-resistant cell line CK2 in comparison to the parental cell line. The results show that EGCG and green tea extract increased the DNA damage in the CK2 cell line during short exposure. The cytotoxicity of EGCG and ECG increased with the time of incubation. Green tea extract induced lipid peroxidation in the CK2 cell line. The pro-oxidant effect of green tea was determined at concentrations higher than those found in traditionally prepared green tea infusions.

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Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Cited by 212 publications

References 37 publications

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

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

Cytotoxic and Genotoxic Effects of the Quercetin/Lanthanum Complex on Human Cervical Carcinoma Cells In Vitro

Genotoxic Effects of Green Tea Extract on Human Laryngeal Carcinoma Cells In Vitro

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