MATERIALS AND METHODS: Considering the ability of SCS to also promote the activity of the antiestrogen, tamoxifen, we further examined the effect of SCS in modulating cell cycle progression and related proteins in MCF-7 and MDA-MB-231 cells alone and in combination with tamoxifen. Expression of cell cycle- related transcripts was analysed based on a previous microarray dataset.
RESULTS: SCS significantly caused G1 arrest of both types of cells, similar to tamoxifen and this was associated with modulation of cyclin D1, p21 and p53. In combination with tamoxifen, the anticancer effects involved downregulation of ERα protein in MCF-7 cells but appeared independent of an ER-mediated mechanism in MDA-MB-231 cells. Microarray data analysis confirmed the clinical relevance of the proteins studied.
CONCLUSIONS: The current data suggest that SCS growth inhibitory effects are similar to that of the antiestrogen, tamoxifen, further supporting the previously demonstrated cytotoxic and apoptotic actions of both agents.
RESULTS: Compared to the non-obese diabetic resistant (NOR) mice, the peritoneal macrophages of NOD mice expressed increased levels of PPARalpha but reduced levels of PPARgamma2, while PPARgamma1 expression was unchanged in all age groups. CD4-positive lymphocytes expressed low levels of PPARalpha in diabetic NOD mice and greatly reduced expression of PPARgamma2 in all age groups. Unlike peritoneal macrophages and CD4-positive cells, the CD8-positive cells expressed low levels of PPARgamma1 in diabetic NOD mice but no difference in PPARalpha and PPARgamma2 expression was observed compared to NOR mice.
CONCLUSION: The current findings may suggest an important regulatory role of PPARs in the pathogenesis of autoimmune diabetes.
MATERIALS AND METHODS: Thirty-five inbred female Sprague Dawley rats aged 43 days were administered with three weekly doses of N-methyl-N-nitrosourea (NMU) intraperitoneally (ip) at 50 mg/kg body weight. Animals were randomized (beginning from 10 mm tumor size) into four TAM-treated (50, 100, 200 and 500 μg/day) groups of six animals each, and another group (n=6) treated with TAM 100 μg/day at starting tumour size of 15 mm. The animals were treated by oral gavage daily for 8 weeks before sacrifice.
RESULTS: Serum urea and creatinine, and overall physical tumor burden were significantly modulated in animals treated with variable doses of TAM compared to the untreated controls (n=5). Final body weight and tumor number were significantly different in the 10 mm-treated animals compared to those treated at 15 mm. There were no significant differences in histopathological features among all the groups.
CONCLUSIONS: Our findings suggest the importance of standardizing tumour size and drug doses before initiation of treatment, particularly in the direct comparison of basic end-tumour physical parameters.
AIM OF THE STUDY: To investigate the potential of F3 from S. crispus to prevent metastasis in breast cancer.
MATERIALS AND METHODS: The antimetastatic effects of F3 were first investigated on murine 4T1 and human MDA-MB-231 breast cancer cell (BCC) lines using cell proliferation, wound healing and invasion assays. A 4T1-induced mouse mammary carcinoma model was then used to determine the expression of metastasis tumor markers, epithelial (E)-cadherin, matrix metalloproteinase (MMP)-9, mucin (MUC)-1, nonepithelial (N)-cadherin, Twist, vascular endothelial growth factor (VEGF) and vimentin, using immunohistochemistry, following oral treatment with F3 for 30 days.
RESULTS: Significant growth arrest was observed with F3 IC50 values of 84.27 µg/ml (24 h) and 74.41 µg/ml (48 h) for MDA-MB-231, and 87.35 µg/ml (24 h) and 78.75 µg/ml (48 h) for 4T1 cells. F3 significantly inhibited migration of both BCC lines at 50 μg/ml for 24 h (p = 0.018 and p = 0.015, respectively). Similarly, significant inhibition of invasion was demonstrated in 4T1 (75 µg/ml, p = 0.016) and MDA-MB-231 (50 µg/ml, p = 0.040) cells compared to the untreated cultures. F3 treatment resulted in reduced tumor growth compared to untreated mice (p