Inhibition of proliferation of T47D human breast cancer cells: alterations in progesterone receptor and p53 tumor suppressor protein.

We have investigated the influence of three structurally different but functionally related compounds [1, 10 ortho-phenanthroline (phenanthroline), Rifampicin and aurin tricarboxylic acid (ATA)] on the rate and the extent of proliferation of progesterone-responsive T47D human breast cancer cells. These compounds have previously been used in this laboratory and have been shown to modulate properties of nucleic acid binding proteins. Because p53 and the progesterone receptor (PR) are both DNA binding proteins that appear to regulate proliferation of breast cells, alterations in T47D cell p53 and PR levels were examined to determine their relevance in cell proliferation. T47D cells were grown in the absence of phenol red and in the presence of 5% fetal calf serum with or without charcoal stripping in the presence of the inhibitors. The rate of proliferation of cells grown in Rifampicin containing medium exhibited nearly 70% inhibition. Phenanthroline, a known metal chelator, was an effective inhibitor of proliferation at 3 mM reducing the cell number by more than 75%. ATA (0.24-2.4 micrograms/ml) inhibited the growth of the cells by nearly 50%. Analysis of the mechanism of action of these compounds revealed that treatment with these compounds caused specific changes in the molecular composition of T47D cell PR. Whereas ATA caused increased stability of PR isoforms, Rifampicin induced a upshift in the mobility of PR in SDS gels-a phenomenon associated with hyperphosphorylation of steroid receptors (SRs). Phenanthroline treatment (> 2 mM) caused a complete down-regulation of PR and the tumor suppressor protein, p53. The downregulation of p53 paralleled the changes in the molecular composition of PR. We propose that the inhibition of T47D cell proliferation by phenanthroline, Rifampicin and ATA results from a number of cellular changes that include regulation of p53 and PR.

Predicting diabetic control from competence, adherence, adjustment, and psychopathology.

OBJECTIVE: To determine what psychological and behavioral factors were most predictive of diabetic control. METHOD: Seventy-nine youths with diabetes were assessed cross-sectionally, using youths' reports of self-esteem, anxiety, and attitudes about diabetes, and parents' reports of competence and psychopathology (from the Child Behavior Checklist) and diabetic adherence as independent variables. Glycosylated hemoglobin A1c was the dependent variable, reflecting diabetic control. After the effects of several background variables were partialed out, a principal-components analysis grouped the substantive variables into three larger components. RESULTS: Among the background variables, duration of illness and family size significantly predicted diabetic control. Among substantive components, Competence/Adherence (including Total Competence, dietary compliance, and frequency of blood glucose checks) was highly predictive of diabetic control, primarily due to the effect of Total Competence. Adjustment (including self-esteem, anxiety levels, and attitudes about diabetes) and Psychopathology were less predictive. A model was constructed showing the relationships between these predictive components and diabetic control. CONCLUSIONS: In this generally well-adjusted sample, that Total Competence, more than other measures, predicted diabetic control suggests it could be used by clinicians to anticipate diabetic youths at risk.

Taxol and cisplatin inhibit proliferation of T47D human breast cancer cells.

We have examined the influence of taxol and cisplatin on the rate and extent of proliferation of T47D cells grown in the presence of 5% fetal bovine serum (FBS). An 8-day exposure of the cells to taxol inhibited the growth completely maintaining the number of cells to the level seen at initial plating. The taxol effect was evident at 10 nM-1 microM concentration and the half maximum inhibition was calculated to be 20 nM taxol. While the cells in the control group taxol-treated group remained at the initial number. Similar observations were made regarding the influence of cisplatin, which caused 80-90% inhibition in the number of the cells. When combined, taxol and cisplatin caused a further inhibition in the proliferation of T47D cells. The results of our studies demonstrate that both taxol and cisplatin, the known antineoplastic agents, block the proliferation of T47D human breast cancer cells effectively and are potentially useful chemotherapeutic agents for the management of breast cancer.