Effect of dietary phytochemicals on cancer development (review)

Vegetables, fruits, and whole grains contain a wide variety of phytochemicals that have the potential to modulate cancer development. There are many biologically plausible reasons why consumption of plant foods might slow or prevent the appearance of cancer. These include the presence in plant foods of such potentially anticarcinogenic substances as carotenoids, chlorophyll, flavonoids, indole, isothiocyanate, polyphenolic compounds, protease inhibitors, sulfides, and terpens. The specific mechanisms of action of most phytochemicals in cancer prevention are not yet clear but appear to be varied. Considering the large number and variety of dietary phytochemicals, their interactive effects on cancer risk may be extremely difficult to assess. Phytochemicals can inhibit carcinogenesis by inhibiting phase I enzymes, and induction of phase II enzymes, scavenge DNA reactive agents, suppress the abnormal proliferation of early, preneoplastic lesions, and inhibit certain properties of the cancer cell.

Supplementation with antioxidants prior to bone marrow transplantation.

Conditioning therapy preceding bone marrow transplantation (BMT) usually consists of high-dose chemotherapy and total body irradiation (TBI). It has acute and delayed toxic effects on several tissues, possibly related to peroxidation processes and exhaustion of antioxidants. Early studies indicated an increase of peroxide processes and a decrease of antioxidants during conditioning therapy. Hence, we investigated the effect of antioxidant supplementation on peroxidation processes and antioxidant status. We supplemented a patient group (N = 16) [BMT (+)], with oral 45 mg beta-carotene, 825 mg alpha-tocopherol and 450 mg ascorbic acid daily for three weeks before conditioning therapy. Another patient group (N = 10), BMT(-), was not supplemented with antioxidants before conditioning therapy. In order to investigate the physiologic effect of supplement antioxidants a healthy control group (N = 10) was supplemented with the same doses as BMT(+). Peroxide concentrations in plasma were measured by using the cholesterol oxidase (CHOD)-iodide method and antioxidants were measured by HPLC. Before supplementation the beta-carotene and alpha-tocopherol concentrations were comparable in both patient groups. After supplementation significantly higher beta-carotene and alpha-tocopherol concentrations were measured in the supplemented patients, BMT(+), than in the unsupplemented patients, BMT(-). After conditioning therapy, BMT(+) patients showed a significantly higher beta-carotene concentration (p < 0.05) than before supplementation. In BMT(-) patients the beta-carotene (p < 0.05) and alpha-tocopherol concentrations (p < 0.01) decreased significantly and the lipid peroxide concentration increased significantly following conditioning therapy. We conclude that antioxidant supplementation prior to conditioning therapy reduces peroxidation processes induced by conditioning therapy in bone marrow recipients.

Dietary modification of brain function: effects on neuroendocrine and psychological determinants of mental health- and stress-related disorders.

Stress is associated with both psychological and biological adaptation. Chronic stress, however, impairs adaptation, and may finally lead to illness, in part through unhealthy changes in nutritional behavior. This chapter shows how physiological and psychological stress responses are affected by different food ingredients, and how stress affects health behavior, for example food choice. It becomes obvious that nutrition is closely linked to food choice and that food ingredients affect a broad range of neuroendocrine and related psychological processes, which regulate adaptation to chronic stress. Thus, dietary modification may become a valuable tool to modify the susceptibility to stress and stress-related disorders.

Pegfilgrastim: a recent advance in the prophylaxis of chemotherapy-induced neutropenia.

Chemotherapy-induced neutropenia is a frequent complication in cancer patients receiving myelosuppressive chemotherapy. Chemotherapy-induced neutropenia can result in febrile neutropenia and potentially life-threatening infections requiring hospitalization and intravenous anti-infectives. Chemotherapy dose may be reduced or delayed as a result of chemotherapy-induced neutropenia, which can negatively impact treatment outcomes. Granulocyte colony-stimulating factors, such as filgrastim, stimulate neutrophil production and can therefore reduce the incidence and severity of chemotherapy-induced neutropenia. Filgrastim undergoes rapid renal clearance and needs to be administered daily. The development of pegfilgrastim represents a significant advance in the management of chemotherapy-induced neutropenia as the longer serum half-life allows once-per-chemotherapy administration, and evidence supports increased prophylactic effectiveness in reducing the incidence of febrile neutropenia. This paper reviews the development of pegfilgrastim and summarizes recent clinical data on the use of this simple, effective and well-tolerated option for the management of chemotherapy-induced neutropenia in patients with cancer.

Effect of methionine on the fatty acid composition of cellular membranes in rats with chronic ethanol consumption and jejunoileal bypass.

The objective of this study was to investigate the effect of alcohol administration on jejunoileal bypass (JIB)-induced liver dysfunction in rats resulting in abnormalities of fatty acid composition of cell membranes, and whether methionine is able to reverse these changes. Male Wistar rats were subjected to a jejunoileal bypass operation. For 12 weeks, all groups were pair-fed either an alcohol-containing (36% of total calories) liquid diet or a liquid diet in which alcohol was replaced isocalorically by starch. Methionine supplementation in three control groups was 0, 32, 160 and 224 mg/kg body weight/day and the rats in the four alcohol feeding groups received 0, 32, 160 and 224 mg/kg body weight/day. In the alcohol group without any methionine supplementation, higher proportions of oleic and linoleic acid and lower proportions of docosahexaenoic and arachidonic acid became evident in tissue samples of liver and jejunum, in comparison with the other alcohol group. A possible explanation for this reduction in tissue polyunsaturated fatty acid (PUFA) may be a decrease in the activities of delta 6-and delta 5-desaturases, and subsequently a displacement of PUFA from lipid fractions by other fatty acids. Interestingly, in the alcohol group with the highest methionine supplementation, compared to all other alcohol groups, lower proportions of oleic acid and higher proportions of docosahexaenoic acid, appeared. A possible explanation for this increase of PUFA in tissue may be increased activities of delta 6- and delta 5-desaturases.

Changes in human serum alcohol dehydrogenase activity during retinoic acid treatment of cancer patients.

Retinoids can inhibit cell growth and induce cell differentiation in experimental tumour models. Human alcohol dehydrogenase (ADH) exists as a group of enzymes that can be placed into five classes based upon structural and functional distinctions. Human class I ADH catalyses the oxidation of a wide variety of alcohols including ethanol and retinol, whereas human class II ADH does not catalyse the oxidation of retinol. Using specific fluorescent substrates, class I and class II ADH activity in human sera was determined. No significant changes in class I or II activity were observed after 4 weeks of treatment with cis-retinoic acid (cRA). While total ADH activity was increased from 84 +/- 78 mU/1 to 206 +/- 70 mU/1 (mean +/- SD, P < 0.02) after 1 week of treatment, there were no further significant changes after 4 weeks of treatment with cRA. Sex-related differences were observed on total ADH activity after 1 week of treatment with cRA. Although total ADH activity of patients with cancer of the cervix increased significantly after 1 week of treatment, there were no significant changes in total activity in head and neck cancer patients. This sex-related difference might be dependent on the stage of the menstrual cycle. The elimination of ethanol in women can be either faster or slower than in men depending on the stage of menstrual cycle. This study therefore suggests that the main ADH activity observed in serum belongs to class II, and not to class I ADH. The data from this study also suggest that retinoic acid has a positive feedback effect on total ADH activity after 1 week of treatment.