Suppressive role of Viola odorata extract on malignant characters of mammosphere-derived breast cancer stem cells.

BACKGROUND: Mammospheres are breast cancer stem cells (BCSCs) that could be yielded through culturing cells in non-adherent and non-differentiating condition. With regard to therapy resistance of cancer stem cells (CSCs), it is essential to discover efficient approaches targeting CSCs. Viola odorata extract has been considered as a traditional herbal anti-metastatic drug in several cancer cells. Effect of this drug on BCSCs has not been clearly identified. Current study tries to detect and to compare effect of Viola odorata extract on malignant characterization of breast cancer cell lines and BCSCs. MATERIALS AND METHODS: MCF7 and SKBR3 and their derived mammospheres as BCSCs were used and the effect of alcoholic extraction of Viola odorata on apoptosis and malignant characters of MCF7, SKBR3 and their derived BCSCs were analyzed and compared. RESULTS: Viola odorata extract induced cell death in MCF7, SKBR3 and their derived mammospheres through apoptosis without any effects on MCF10A. Also, this extract showed anti-migratory, anti-invasion and anti-colony formation activity in MCF7, SKBR3 and their derived mammospheres which was significantly more in MCF7- and SKBR3-derived mammospheres. Also, this extract decreased size and volume of tumors generated by MCF7, SKBR3 and their derived mammospheres in chicken embryo model. CONCLUSION: Viola odorata extract exerted anti-cancerous activity on both breast cancer cell lines and their derived BCSCs. Anti-cancerous activity of this extract was significantly more in MCF7-, SKBR3-derived mammospheres in comparison with dedicated cell lines. Data suggest that Viola odorata extract mostly targets cancerous cells, not normal cells with exception in high concentration. It acts in a cell-dependent manner.

Biopharmaceutical characterization of oral theophylline and aminophylline tablets. Quantitative correlation between dissolution and bioavailability studies.

Considering the narrow therapeutic index of theophylline and the low range between the safe and toxic serum concentrations of this drug, the study of its pharmacokinetic properties is necessary. However, considering the time consuming and expensive in vivo tests, quantitative correlation between in vivo bioavailability and in vitro dissolution tests can be used routinely in quality control tests of these drug products to predict the in vivo pharmacokinetic parameters. For this reason healthy human volunteers were used for in vivo studies and serum samples were analyzed by a fluorescence polarization immunoassay analysis (FPIA) method. The results showed that an open one compartmental model could best describe the pharmacokinetic properties of orally administered theophylline and aminophylline tablets. Linear regression analysis by least-square method showed a good correlation between some in vivo and in vitro parameters obtained from dissolution studies by rotating basket and paddle methods. D(30)% (percentage of drug dissolved in vitro after 30 min) and F(0.5)% (drug absorbed in vivo after half an hour calculated by Wagner-Nelson equation) showed best correlation (r=0. 99036). C(max) (maximum serum concentration) of this drug also correlates well with t(25%) (time required to dissolve 25% of the drug). The calculated correlation coefficients could best predict the actual values of some pharmacokinetic parameters; AUC(0-->infinity), AUC(0-->1), F(0.5)% and C(max).

Zinc-induced inhibition of insulin secretion from isolated rat islets of Langerhans.

The present experiments indicate that ZnCl2 (0.015-0.50 mM) inhibits in a dose-dependent manner insulin secretion from isolated rat islets stimulated by D-glucose, L-leucine, and potassium. This inhibitory effect is partially reversed by washing and antagonized by high calcium concentrations in the medium. Zinc levels that inhibit insulin release do not affect 45calcium uptake, and zinc will not replace calcium in triggering insulin release. The conversion of 14C-D-glucose to 14CO2 by islets is not modified by zinc (0.12 mM or 0.50 mM) following either 2- or 0.5-h incubation periods, respectively. It is concluded that the inhibitory effect of zinc on insulin secretion may, in part, be mediated through interference with an intracellular function of calcium by the beta-cell.

Chromium-induced inhibition of insulin secretion from isolated islets of Langerhans.

CrCl3, 0.25, 0.5, 1.0, and 1.5 mmol/l inhibited glucose-induced insulin secretion in a reversible and dose dependent manner. Cr also inhibited basal secretion of insulin in the presence of 5.5 mmol/l glucose and insulin secretion stimulated by 50 mmol/l K+ or 15 mmol/l L-leucine. When 2 mmol/l theophylline was employed to potentiate the stimulatory effect of 16.5 mmol/l glucose, the inhibitory effect of 1.5 mmol/l Cr was reduced and that of 0.5 mmol/l virtually abolished. A similar reduction in the inhibitory effect of Cr was observed when the medium calcium concentration was increased from 2.5 to 5, 7.5 and 12.5 mmol/l. Cr did not alter the conversion of 14C-glucose to 14CO2 or 45Ca uptake by isolated islets. It is concluded that the inhibitory effect of Cr on insulin secretion may be mediated through interference with an intracellular function of Ca++ in the beta cell.

Chromium-induced hyperglycemia in the rat.

The acute administration of chromium chloride (Cr) produces hyperglycemia in rats. Adrenalectomy prevents the hyperglycemic effect but not the glucose intolerance. Subacute exposure of rats to Cr for 7--23 days does not change the resting blood glucose nor is there an acute or subacute effect on tolerance to glucose load. Administration of Cr does not influence acute insulin hypoglycemia. Thus contrary to Cr deficient animal, at the concentrations tested, Cr appears to be a hyperglycmiec agent to rats with minimal subacute effects.

Antagonism of cadmium and alloxan-induced hyperglycemia in rats by Trigonella foenum graecum.

This study was stimulated by popular belief that Trigonella foenum graecum has antidiabetic activity in which the hypoglycemic effect has been confirmed by several investigators. However, the mode of action appears to be unclear. To gain some insight, the stems and leaves of the plant as well as the known active seeds were extracted at room temperature (ca 20 C) for three days with water or acetone and by soxhlet 70 C, and tested by oral administration to rats. Acetone and CC14 extracts before use, were evaporated below 30 C under vacuo, and the residue dissolved in distilled water containing Tween 80. Hypoglycemic activity of these extracts were tested on 20 hour fasted normal, alloxan and cadmium treated rats. The latter has been shown to cause hyperglycemia by releasing epinephrine in intact rats and inhibiting insulin release in the isolated perfused rat pancreas. Results showed that with seeds the CC14, soxhlet acetone extracts were inactive in normal animals as were the water and acetone extracts of stems and leaves. These observations may be compared with room temperature acetone extraction of seeds which exhibited what appeared to be dose related hypoglycemic effects. The hyperglycemia induced by cadmium or alloxan was antagonized by room temperature acetone seed or stem and leaves extracts. Tentative interpretation of the above results, are that Trigonella acetone extract appears to act, at least in part, at the cellular level to produce its hypoglycemic effects on normal rats or those as treated with cadmium or alloxan.