Differential sensitivity of various human tumour-derived cell types to apoptosis by organic derivatives of selenium

Jariwalla, Raxit J.; Gangapurkar, Bhakti; Nakamura, Daniel

doi:10.1017/s0007114508998305

Cited by 46 publications

(28 citation statements)

References 23 publications

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“…Glutathione peroxidase and thioredoxin reductase cofactor; antioxidant (46,93,753) ; constituent of selenoproteins (754) ; tumour growth (46,110,754,755) ; prostate and colon cancer (cited in Reeves et al (633) ); susceptibility to carcinogens (756,757) ; apoptotic effects (758) ; anti-carcinogenic (759) ; cell membranes and oxidation damage (760) ; anti-infective (761,762) ; plasma, liver and erythrocyte GSH peroxidase activity (763) ; insulin resistance and vascular endothelium (764,765) ; platelet aggregation (753) P (204,603,766) : Kidney health (766,767) ; colorectal adenoma (768) ; tooth development (769) Ca (204,603) :…”

Section: Appendixmentioning

confidence: 99%

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

2010

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Epidemiological studies have clearly shown that whole-grain cereals can protect against obesity, diabetes, CVD and cancers. The specific effects of food structure (increased satiety, reduced transit time and glycaemic response), fibre (improved faecal bulking and satiety, viscosity and SCFA production, and/or reduced glycaemic response) and Mg (better glycaemic homeostasis through increased insulin secretion), together with the antioxidant and anti-carcinogenic properties of numerous bioactive compounds, especially those in the bran and germ (minerals, trace elements, vitamins, carotenoids, polyphenols and alkylresorcinols), are today well-recognised mechanisms in this protection. Recent findings, the exhaustive listing of bioactive compounds found in whole-grain wheat, their content in whole-grain, bran and germ fractions and their estimated bioavailability, have led to new hypotheses. The involvement of polyphenols in cell signalling and gene regulation, and of sulfur compounds, lignin and phytic acid should be considered in antioxidant protection. Whole-grain wheat is also a rich source of methyl donors and lipotropes (methionine, betaine, choline, inositol and folates) that may be involved in cardiovascular and/or hepatic protection, lipid metabolism and DNA methylation. Potential protective effects of bound phenolic acids within the colon, of the B-complex vitamins on the nervous system and mental health, of oligosaccharides as prebiotics, of compounds associated with skeleton health, and of other compounds such as a-linolenic acid, policosanol, melatonin, phytosterols and para-aminobenzoic acid also deserve to be studied in more depth. Finally, benefits of nutrigenomics to study complex physiological effects of the 'whole-grain package', and the most promising ways for improving the nutritional quality of cereal products are discussed. Whole-grain wheat: Bioactive compounds: Physiological mechanisms: Health IntroductionThere is growing evidence that whole-grain cereal products protect against the development of chronic diseases. The most important of these in terms of public health are obesity (1,2) , the metabolic syndrome (3,4) , type 2 diabetes (5,6) , CVD (7) and cancers (8 -12) . Whole-grain cereal consumption has also been shown to be protective against mortality, as was shown with inflammation-related death (i.e. noncardiovascular and non-cancer inflammatory diseases such as, for example, respiratory system diseases) (13) and with cancer and CVD (4,14,15) . These conclusions are supported by the effects of consuming refined cereal products (bread, pasta and rice), as these have been associated with an increased risk of digestive tract, pharynx, larynx and thyroid cancers in northern Italians (16) . However, an association between a lower risk of developing a chronic disease and a high whole-grain cereal consumption does not mean a direct causal relationship and provides no information about the physiological mechanisms involved.These metabolic diseases are related to our daily lifestyle, no...

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Section: Appendixmentioning

confidence: 99%

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

2010

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“…Various forms of selenium compounds have been shown to possess apoptosis-inducing and anti-proliferative effects, and are thus considered as potential chemopreventive and chemotherapeutic agents for cancer [4], [5], [6]. In this study, we tested whether incorporating selenium into TMZ would improve the anticancer properties of this drug.…”

Section: Introductionmentioning

confidence: 99%

Rational Incorporation of Selenium into Temozolomide Elicits Superior Antitumor Activity Associated with Both Apoptotic and Autophagic Cell Death

Cheng

Zhang

et al. 2012

PLoS ONE

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Background The DNA alkylating agent temozolomide (TMZ) is widely used in the treatment of human malignancies such as glioma and melanoma. On the basis of previous structure-activity studies, we recently synthesized a new TMZ selenium analog by rationally introducing an N -ethylselenocyanate extension to the amide functionality in TMZ structure. Principal Findings This TMZ-Se analog showed a superior cytotoxicity to TMZ in human glioma and melanoma cells and a more potent tumor-inhibiting activity than TMZ in mouse glioma and melanoma xenograft model. TMZ-Se was also effective against a TMZ-resistant glioma cell line. To explore the mechanism underlying the superior antitumor activity of TMZ-Se, we compared the effects of TMZ and TMZ-Se on apoptosis and autophagy. Apoptosis was significantly increased in tumor cells treated with TMZ-Se in comparison to those treated with TMZ. TMZ-Se also triggered greater autophagic response, as compared with TMZ, and suppressing autophagy partly rescued cell death induced by TMZ-Se, indicating that TMZ-Se-triggered autophagy contributed to cell death. Although mRNA level of the key autophagy gene, Beclin 1 , was increased, Beclin 1 protein was down-regulated in the cells treated with TMZ-Se. The decrease in Beclin 1 following TMZ-Se treatment were rescued by the calpain inhibitors and the calpain-mediated degradation of Beclin1 had no effect on autophagy but promoted apoptosis in cells treated with TMZ-Se. Conclusions Our study indicates that incorporation of Se into TMZ can render greater potency to this chemotherapeutic drug.

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“…However, effects of more subtle changes in Se status are less well defined and definition of the functions and underlying mechanisms is lacking. Se has been shown to cause immune response promotion [9] and cytokine production [10], and in contrast, immune response inhibition [11], and induction of cell death or apoptosis [12]–[14].…”

Section: Introductionmentioning

confidence: 99%

Selenium Promotes T-Cell Response to TCR-Stimulation and ConA, but Not PHA in Primary Porcine Splenocytes

et al. 2012

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There is controversy in the literature over whether the selenium (Se) influences cellular immune responses, and the mechanisms possibly underlying these effects are unclear. In this study, the effects of Se on T-cell proliferation and IL-2 production were studied in primary porcine splenocytes. Splenocytes were treated with different mitogens in the presence of 0.5–4 µmol/L sodium selenite. Se significantly promoted T-cell receptor (TCR) or concanavalin A (ConA)-induced T-cell proliferation and IL-2 production but failed to regulate T-cell response to phytohemagglutinin (PHA). In addition, Se significantly increased the levels of cytosolic glutathione peroxidase (GPx1) and thioredoxin reductase 1 (TR1) mRNA, the activity of GPx1 and the concentration of reduced glutathione (GSH) in the unstimulated, or activated splenocytes. These results indicated that Se improved the redox status in all splenocytes, including unstimulated, TCR, ConA and PHA -stimulated, but only TCR and ConA-induced T-cell activation was affected by the redox status. N-acetylcysteine (NAC), a pharmacological antioxidant, increased T-cell proliferation and IL-2 production by TCR and ConA stimulated splenocytes but had no effect on the response to PHA in primary porcine splenocytes confirming that PHA-induced T-cell activation is insensitive to the redox status. We conclude that Se promotes GPx1 and TR1 expression and increases antioxidative capacity in porcine splenocytes, which enhances TCR or ConA -induced T-cell activation but not PHA-induced T-cell activation. The different susceptibilities to Se between the TCR, ConA and PHA -induced T-cell activation may help to explain the controversy in the literature over whether or not Se boosts immune responses.

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Differential sensitivity of various human tumour-derived cell types to apoptosis by organic derivatives of selenium

Cited by 46 publications

References 23 publications

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

New hypotheses for the health-protective mechanisms of whole-grain cereals: what is beyond fibre?

Rational Incorporation of Selenium into Temozolomide Elicits Superior Antitumor Activity Associated with Both Apoptotic and Autophagic Cell Death

Selenium Promotes T-Cell Response to TCR-Stimulation and ConA, but Not PHA in Primary Porcine Splenocytes

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