Tricin, a flavone found in rice bran, inhibits the growth of human-derived malignant MDA-MB-468 breast tumour cells at submicromolar concentrations. As part of the exploration of tricin as a potential cancer chemopreventive agent, we investigated the duration and cell cycle specificity of growth inhibition elicited by tricin in vitro and the effect of tricin on the development of MDA-MB-468 tumours grown in immune-compromised MF-1 mice in vivo. Preincubation of MDA-MB-468 cells with tricin (1 -40 mM) for 72 h compromised cell growth after tricin removal, and such irreversibility was not observed in human breast-derived nonmalignant HBL-100 cells. Tricin (X5 mM) arrested MDA-MB-468 cells in the G2/M phase of the cell cycle without inducing apoptosis as adjudged by annexin V staining. In nude mice consumption of tricin with the diet (0.2%, w w À1 ) from 1 week prior to MDA-MB-468 cell implantation failed to impede tumour development. Steady-state levels of tricin in plasma, breast tumour tissue and intestinal mucosa, as measured by HPLC, were 0.13 mM and 0.11 and 63 nmol g À1 , respectively. Cells were exposed to tricin (0.11, 1.1 or 11 mM) in vitro for 72 h and then implanted into mice. The volume of tumours in animals bearing cells pre-exposed to 11 mM tricin was less than a third of that in mice with control cells, while tumours from cells incubated with 0.1 or 1.1 mM tricin were indistinguishable from controls. These results suggest that the potent breast tumour cell growth-inhibitory activity of tricin in vitro does not directly translate into activity in the nude mouse bearing the MDA MB-468 tumour. While the results do not support the notion that tricin is a promising candidate for breast cancer chemoprevention, its high levels in the gastrointestinal tract after dietary intake render exploration of its ability to prevent colorectal carcinogenesis propitious.
Role demands of caring for a young child were high for all participants, particularly if the child had a disability. Participants seemed to respond to these demands by giving up other discretionary roles in order to meet their caregiving obligations. Thus, asking mothers of children with disabilities to take on therapy-related caregiving tasks may contribute to role strain.
NMR-visible mobile lipid (ML) has been observed in aggressive tumors and also in in vitro tumor cell models subjected to growth-inhibiting conditions, such as confluence or low-pH stress. The aim of the present study was to determine if ML production after confluence or low pH stress in a cultured cell model of brain tumor is due to growth arrest alone. ML was observed in situ by one- and two-dimensional (1)H NMR in viable but growth-arrested C6 glioma cells superfused for a period of 48 h after harvesting. The rate of ML production in cells harvested at subconfluence was compared to the rate in cells confluent for one cell cycle and to the rate in subconfluent-harvested cells superfused at low pH (pH 6.1). Confluent-harvested cells produced ML at a markedly greater rate than that of cells harvested at subconfluence, suggesting the involvement of prior cell-cell contact rather than simple growth arrest. A high rate was also observed in subconfluent-harvested cells subjected to low pH, indicating that ML in pH-stressed cells also does not arise from growth arrest alone. Furthermore, two-dimensional data on the degree of unsaturation of the ML fatty acyl chains and one-dimensional (31)P and two-dimensional (1)H NMR data on the GPC content of the cells suggest distinct metabolic pathways for the production of ML following confluence and low-pH stress.
A cell surface UDP-galactose:N-acetylglucosamine galactosyltransferase (GT) has been directly localized on bovine cells in tissue culture by immunohistochemical techniques. A conventional rabbit heteroantiserum was prepared against an affinity-purified soluble form of GT from bovine milk, and a monospecific IgG fraction was isolated by affinity chromatography on a GT adsorbent. As demonstrated by indirect immunofluorescence, antigen to this antibody is present on the surface of all three bovine cell lines tested. It was uniformly distributed over the exposed membrane surface of fixed cells. Exposure of living cells to the anti-GT antibody resulted in its time-dependent aggregation in the plane of the membrane. Antigen (GT) was released from the membrane surface by trypsin digestion, and its reappearance required protein synthesis, since cycloheximide effectively prevented repopulation of the cell surface.
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