Regulation of iodine-glucose flip-flop in SW1736 anaplastic thyroid cancer cell line.

AIMS AND BACKGROUND: The alternative manner of iodide and glucose uptake found in different types of thyroid cancer, referred to flip-flop. ATC cells indicate low iodide uptake and high glucose uptake, which lack the morphology and genetic characteristics of well-differentiated tumors and become increasingly invasive. Importance placed on the discovery of innovative multi-targeted medicines to suppress the dysregulated signaling in cancer. In this research, we aimed to clarify molecular mechanism of Rutin as a phytomedicine on anaplastic thyroid cancer cell line based on iodide and glucose uptake. MATERIAL METHODS: The MTT test was employed to test cell viability. Iodide uptake assay was performed using a spectrophotometric assay to determine iodide uptake in SW1736 cells based on Sandell-Kolthoff reaction. For glucose uptake detection, ''GOD-PAP'' enzymatic colorimetric assay was applied to measure the direct glucose levels inside of the cells. Determination of NIS, GLUT1 and 3 mRNA expression in SW1736 cells was performed by qRT-PCR. Determination of NIS, GLUT1 and 3 protein levels in SW1736 cells was performed by western blotting. RESULTS: According to our results, Rutin inhibited the viability of SW1736 cells in a time- and dose-dependent manner. Quantitative Real-time RT-PCR analysis exposed that NIS mRNA levels were increased in Rutin treated group compared to the control group. Accordingly, western blot showed high expression of NIS protein and low expression of GLUT 1 and 3 in Rutin treated SW1736 cell line. Rutin increased iodide uptake and decreased glucose uptake in thyroid cancer cell line SW1736 compared to control group. CONCLUSION: Multiple mechanisms point to Rutin's role as a major stimulator of iodide uptake and inhibitor of glucose uptake, including effects at the mRNA and protein levels for both NIS and GLUTs, respectively. Here in, we described the flip-flop phenomenon as a possible therapeutic target for ATC. Moreover, Rutin is first documented here as a NIS expression inducer capable of restoring cell differentiation in SW1736 cell line. It also be concluded that GLUTs as metabolic targets can be blocked specifically by Rutin for thyroid cancer prevention and treatment.

Study of the effect of aqueous extract of Grewia tenax fruit on iron absorption by everted gut sac.

Grewia tenax roots, leaves, juice and fruit decoctions have been used in Africa and Southeast Asiatic countries for a variety of medical purposes. In this investigation, we report the effect of aqueous extract of Grewia tenax fruit (AEGTF) on the variation in vitro of iron absorption. The incubation of freshly prepared rat everted gut sac (EGS) in Ringer medium containing FeSO(4) in the absence of AEGTF showed that in stomach there is iron absorption only at 15 min of incubation time, whereas, at duodenum and jejunum, iron uptake occurs just after 1 min of incubation time and the maximum of iron absorption is registered at 15 min of incubation time. Addition of AEGTF at different concentrations favors significantly this iron transfer from the mucous side toward the serous one. The maximum of iron absorption was carried out in the presence of AEGTF at 10 mg/ml and 5 min of incubation time in stomach, duodenum and jejunum. AEGTF used at high doses (20 and 30 mg/ml) reduced significantly iron uptake suggesting a probable toxic effect of this extract. Histological studies confirmed the presence of cytotoxic signs as multinucleated giant cells and the disappearance of enterocyte border brush. With the aim of elucidating the mechanism of action of AEGTF, we are attempting to isolate the active principles present in this extract.

The effect of chromium on parameters related to iron metabolism.

The effect of chromium on some parameters related to iron metabolism was investigated. Preliminary experiments showed that this metal ion was taken up by serum proteins and was dependent on the amount of chromium present in the medium. It was also shown that the uptake of iron was reduced significantly in the presence of chromium. In vivo study showed that the serum levels of iron and total iron binding capacity (TIBC) were reduced by 28 and 11%, respectively, following daily administration of chromium (1 mg/kg) for 45 d. Serum ferritin was reduced by 22% under this condition. Hematocrit and hemoglobin levels were also affected in chromium-treated animals and were both reduced by 17%. Spectrophotometric titration of each individual amino acid located in the iron binding site of transferrin revealed that tyrosine might be the most suitable ligand for the binding of chromium to transferrin. These results suggest that chromium may compete with iron in binding to apo-transferrin, and influence iron metabolism and its related biochemical parameters.

Comparative binding study of aluminum and chromium to human transferrin. Effect of iron.

The characteristics of aluminum and chromium binding to apo-transferrin (apo-tf) have been investigated and compared. Both metal ions were taken up by human transferrin forming complexes with the maximum absorbances at 405 nm for chromium-transferrin (cr-tf) and 240 nm for aluminum-transferrin (Al-tf). In the presence of citric acid, chromium binding to transferrin is five times more than aluminum. The binding of aluminum or chromium to apo-transferrin was reduced by 18 and 22% in the presence of 200 ng/mL of iron. The binding of both metals to apo-tf appears to be pH dependent. In acidic pHs, less chromium and more aluminum binding occurred.

Protective effects of selenium and zinc on changes in catecholamine levels of brain regions in lead intoxified rat.

Lead is a common environmental toxic element for almost all biological systems. The nervous system is the primary target for the lead exposure. In the past few years, increasing considerations have been given to investigate the interaction occurring between toxic metals and some essential metals including Se and Zn with Pb. It has been shown that some trace elements could reverse the toxicity of lead on tissue functions. In this study the protective effects of Zn and Se on lead toxicity were investigated. Results of short time study showed that, intrapritoneal administration of Pb (13.5 mg kg(-1)) daily for 2 weeks reduced the catecholamine levels of cortex by 25, mid-Brain by 21 and cerebellum by 25.6%, respectively. Administration of the same amount of lead in combination with either Zn (0.5 mg kg(-1)) or Se (0.4 mg kg(-1)) reduced catecholamine levels of cortex by 8.3 and 18.3, mid-brain by 6, 10.9 and cerebellum 23, 6% respectively. Daily administration of lead alone (4 mg kg(-1)) for 60 days reduced catecholamine level of cortex by 27.4 and mid-Brain by 47.8 and cerebellum by 39%, respectively. When the same amount of lead in combination with Zinc (0.5 mg kg(-1)) and/or Se (0.4 mg kg(-1)) was administration daily for 60 days, results showed that catecholamine level of cortex was reduced by 9, 20 and mid-brain by 22.6, 29 and cerebellum 25, 16%, respectively. It is concluded that lead reduced catecholamine levels in different brain regions and Zn or Se might be able to reverse this reduction and protect brain function to some extent from lead toxicity.