Antioxidant and Prooxidant Effects of Phenolics on Pancreatic β-Cells in Vitro

Lapidot, Tair; Walker, Michael D.; Kanner, Joseph

doi:10.1021/jf020615a

Cited by 185 publications

(109 citation statements)

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“…For example, hydrogen peroxide is generated in simian virus 40-transformed hamster pancreatic b-cells (HIT) in the presence of 50 mM quercetin or chrysin, 21) and ROS are generated in human thymoma-derived cells (HPB-ALL) in the presence of 50 mM quercetin 39) and in Jurkat cells in the presence of 110-880 mM baicalin (baicalein 7-b-D-glucopyranosiduronate). 40) As shown above, our observations show that ROS are generated in normal human cells in the presence of flavonoids.…”

Section: Discussionmentioning

confidence: 99%

“…16) Further, it has been reported that they exert cytotoxicity at higher concentrations and in the presence of oxidation-catalyzing factors such as transition metal ions. The cytotoxicity of flavonoids toward human promyelocytic leukemia cells (HL-60), 17) human acute myelogeneous leukemia cells (KG1, KG1a, THP-1, and U937), 18) rhesus monkey kidney cells (LLC-MK2), rat glial tumor cells (C6), 19) bovine leukemia virus-transformed lamb embryo kidney fibroblasts (FLK), 20) mouse and hamster pancreatic b-cells (b TC1 and HIT), 21) human fibroblasts (HFK-2), human keratinocytes (HaCaT), human breast cancer adenocarcinoma cells (MCF-7), human neuroblastoma cells (SHEP and WAC-2), and bovine capillary endothelial cells 22) has been found. As shown above, however, there are only a few reports on the cytotoxicity of flavonoids toward human normal cells.…”

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confidence: 99%

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Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Matsuo

Sasaki

Saga

et al. 2005

Biological & Pharmaceutical Bulletin

215

145

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Flavonoids are a group of plant polyphenols and are ubiquitously found in plants. 1,2) Fruits and vegetables, as well as popular beverages such as wine, tea, and coffee, are the main dietary sources of flavonoids. It has been reported that flavonoids show pharmacological effects such as antioxidant, 3,4) antiviral, 5) antitumor, 6) and antiinflammatory activities. 7) In particular, their antioxidant activity has attracted much attention as a possible dietary preventive against cardiovascular and neurodegenerative diseases. 6,8) There are many reports that flavonoids act as antioxidants and protect various cell types from oxidative stress-mediated cell injury. We reported that flavonoids have protective effects on human umbilical vein endothelial (HUVE) cells and rat neuronal cells (PC12) exposed to the highly toxic lipid peroxide linoleic acid hydroperoxide. [9][10][11] In addition, it has been observed that flavonoids suppress the cytotoxicity of hydrogen peroxide toward Chinese hamster cells (V79) 12) and oxidized low-density lipoproteins in human lymphoid cell lines, 13) glucose oxidase-mediated apoptosis in mouse thymocytes, 14) and metal-induced lipid hydroperoxide-dependent lipid peroxidation in a-linoleic acid-loaded rat hepatocytes. 15)On the other hand, it has been suggested that flavonoids act as mutagens, prooxidants, and enzyme inhibitors.16) Further, it has been reported that they exert cytotoxicity at higher concentrations and in the presence of oxidation-catalyzing factors such as transition metal ions. The cytotoxicity of flavonoids toward human promyelocytic leukemia cells (HL-60), 17) human acute myelogeneous leukemia cells (KG1, KG1a, THP-1, and U937), 18) rhesus monkey kidney cells (LLC-MK2), rat glial tumor cells (C6), 19) bovine leukemia virus-transformed lamb embryo kidney fibroblasts (FLK), 20) mouse and hamster pancreatic b-cells (b TC1 and HIT), 21) human fibroblasts (HFK-2), human keratinocytes (HaCaT), human breast cancer adenocarcinoma cells (MCF-7), human neuroblastoma cells (SHEP and WAC-2), and bovine capillary endothelial cells 22) has been found. As shown above, however, there are only a few reports on the cytotoxicity of flavonoids toward human normal cells.If flavonoids are used as dietary factors for health maintenance, relatively large amounts may be ingested. Thus the potentially toxic effects of excessive flavonoid intake must be clarified. 16) In the present paper, we describe the cytotoxicity of nine flavonoids, including the two flavones apigenin and luteolin, the three flavonols 3-hydroxyflavone, kaempherol, and quercetin, the flavonol glycoside rutin, the two flavanones eriodictyol and naringenin, and the flavanol taxifolin (Table 1 and Fig. 1), toward cultured normal human cells, TIG-1 cells and HUVE cells. Further, we examined the intracellular levels of ROS in flavonoid-treated TIG-1 cells using DCF-DA 23) and their incorporation of flavonoids in culture medium. The cytotoxicity of flavonoids, including apigenin, eriodictyol, 3-hydroxyflavone, kaempherol, luteolin,...

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Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Matsuo

Sasaki

Saga

et al. 2005

Biological & Pharmaceutical Bulletin

215

145

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“…Chrysin (5,7-dihydroxyflavone) is a natural flavonoid presented in many plant extracts, including blue passion flower (Passiflora caerulea), honey and propolis (10). A number of studies have shown that chrysin has multiple biological activities, such as antiinflammation, antioxidation and anticancer effects (11)(12)(13). Chrysin has been reported to induce apoptosis in a panel of cancer cell lines, including HeLa cervical cancer cells, U937, HL-60 and L1210 leukemia cells (14).…”

Section: Introductionmentioning

confidence: 99%

Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer cells

et al. 2012

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Abstract. The antitumor activity of 7-piperazinethylchrysin (7-PEC) was investigated in HCT-116 human colon cancer cells. MTT assay revealed that the IC 50 of 7-PEC in HCT-116 cells was 1.5 µM after 72 h of treatment, much lower than that of chrysin (>100 µM). The data showed that 7-PEC was able to inhibit the growth of HCT-116 cells in a concentration-and time-dependent manner. Topical morphological changes of apoptotic body formation after 7-PEC treatment were observed by Hoechst 33258 staining. 7-PEC reduced mitochondrial membrane potential (∆Ψm) of cells in a concentration-dependent manner and increased the production of intracellular reactive oxygen species (ROS). After treatment with 7-PEC, a significant increase of Bax protein expression and decrease of Bcl-2 protein expression were observed at the same time. These events paralleled with activation of p53, caspase-3 and -9 and the release of cytochrome c (cyt-c), as well as poly(ADPribose) polymerase-1 (PARP1) cleavage and downregulation of p-Akt. However, the apoptosis induced by 7-PEC was blocked by Ac-DEVD-CHO, a caspase-3 inhibitor. These results demonstrate that 7-PEC-induced mitochondrial dysfunction in HCT-116 human colon cancer cells triggers events responsible for caspase-dependent apoptosis pathways, and the elevated ratio of Bax/Bcl-2 is likely involved in this effect.

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“…As a result, artifactual bioactivity could be generated (increased glycerol release and lipolysis) by use of this method for testing plant extracts. Lapidot et al [44][45] examined in greater details the possibility of phenolics in apple extracts interacting with components in the cell culture media that resulted in the generation of hydrogen peroxide (H 2 O 2 ). This newly formed product was found to cause the inhibition of the proliferation of tumor cells in vitro.…”

Section: Interpretation Of the Screening Results -Keep Or Drop?mentioning

confidence: 99%

Preparation of Botanical Samples for Biomedical Research

Liu

2008

EMIDDT

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Plants are chemical storehouses, a fact which has driven countless multidisciplinary quests for bioactive compounds. As the very first step of botanical research, the whole desire is to find "hit" plants with specific bioactivities. It is logical to use some strategies that can maximize the chances of finding these "hits" with limited time and resources. In addition to selecting the right plants for screening, how the plant extracts are prepared can also influence the bioactivity screening outcomes. An extract from the same plant material can be quite different in chemical composition having different preparations. Because of the complex mixture nature of plant extracts, it is possible artifact activities may be observed. Thus confirmatory activity tests are often necessary to warrant the next laborious isolation step. A bioassay directed isolation approach may be the most efficient in identifying the bioactive compounds because of the narrowed focus at each isolation step, but a phytochemistry isolation approach is appropriate to characterize a purified bioactive extract. In fact, these two approaches can be taken intermittently whenever efficiency can be improved. Finally, use of the identified active compounds is now broader. In addition to determining a lead compound to continue a drug development path, there is an increasing interest in support for the use of botanical extracts as botanical drugs. Instead of dropping the extract after extracting the lead compound, the natural analogues representing the purified extract now have a chance to become leading compounds in the pursuit of novel therapies for metabolic syndrome and other diseases.

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Antioxidant and Prooxidant Effects of Phenolics on Pancreatic β-Cells in Vitro

Cited by 185 publications

References 50 publications

Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Cytotoxicity of Flavonoids toward Cultured Normal Human Cells

Induction of apoptosis by 7-piperazinethylchrysin in HCT-116 human colon cancer cells

Preparation of Botanical Samples for Biomedical Research

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