Synergistic effect of selenium and genipin triggers viability of 3T3 cells on PVA/Gelatin scaffolds.

PURPOSE: The aim of this study was to reveal the first time synergistic effect of GP and selenium (Se) on 3T3 cells seeded on natural and non-cytotoxic porous scaffolds with poly(vinyl alcohol) (PVA) and gelatin (GE). METHODS: Electrospinning scaffolds were produced as PVA/GE/GA crosslinked with glutaraldehyde (GA) and freeze/dried scaffolds crosslinked with genipin (GP) were divided into two groups as PVA/GE/GP5 and PVA/GE/GP8. The scaffolds were investigated in terms of pore morphology, swell ratio, biodegradation, and biocompatibility. The biocompatibility of the material was tested in vitro by MTT assay on 1, 2, and 3 days to test the cell viability of 3T3 cells. RESULTS: It was observed that Se triggered the excellent cell growth and proliferation on electrospinning and freeze drying PVA/GE scaffolds. CONCLUSIONS: Selenium with PVA/GE scaffolds can be a promising candidate for wound healing application, as it significantly increases cell viability on scaffolds. It is thought that the synergistic effect of selenium with genipin may be an important step in tissue engineering applications. The preliminary study can be supported by in vivo studies in the future.

The effect of iron on the expression levels of calcium related gene in cisplatin resistant epithelial ovarian cancer cells.

Aim: Anticancer drugs (chemotherapeutics) used in cancer treatment (chemotherapy) lead to drug resistance. This study was conducted to investigate the possible effect of iron on calcium homeostasis in epithelial ovarian cancer cells (MDAH-2774) and cisplatin-resistant cells of the same cell line (MDAH-2774/DDP). Methods: To develop MDAH-2774/DDP cells, MDAH-2774 (MDAH) cells were treated with cisplatin in dose increases of 5 µM between 0 µM and 70 µM. The effect of iron on the viability of MDAH and MDAH/DDP cells was determined by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide test at the end of 24 h incubation. Results: At increasing iron concentrations in MDAH and MDAH/DDP cells, the mRNA gene of fifteen genes [inositol 1,4,5-triphosphate receptor (IP3R)1/2/3, ryanodine receptor (RYR)1/2, sarco/endoplasmic reticulum Ca2+ ATPase (SERCA)1/2/3, Na+/Ca2+ exchange (NCX)1/2/3, and plasma membrane Ca2+ ATPase (PMCA)1/2/3/4] associated with Ca2+ differences in expression were determined by quantitative reverse transcription-polymerase chain reaction. Changes in IP3R2, RYR1, SERCA2, NCX3, PMCA1, and PMCA3 gene expressions were observed in iron treatment of MDAH/DDP cells, while changes were detected in iron treatment of MDAH cells in IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX2/3, and PMCA1 expressions. Conclusions: This changes in the expression of calcium channels, pumps, and exchange proteins in the epithelial ovarian cancer cell line and in cisplatin-resistant epithelial ovarian cancer cells suggest that iron may have an important role in regulating calcium homeostasis. Due to differences in the expression of genes that play of an important role in the regulation of calcium homeostasis in the effect of iron, drug resistance can be prevented by introducing a new perspective on the use of inhibitors and activators of these genes and thus cytostatic treatment strategies.

Iron alters Ca2+ homeostasis in doxorubicin-resistant K562 cells.

Iron is an essential trace element especially in cell proliferation, and growth for various cellular events. An increasing amount of research has shown that iron metabolism is altered in tumour cells which usually have rapid growth rates. However, the number of studies on iron metabolism, and calcium regulation are limited in drug-resistant tumour cells. Previously, we have shown that modulation of iron metabolism through iron chelation regulated the intracellular calcium, and increased the doxorubicin sensitivity. In the present study, we investigated the effects of iron on mRNA expression profiles of fifteen key genes (IP3 R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) related to calcium homeostasis in the parental cell line K562 and its subclone doxorubicin-resistant K562 cells. According to the ΔΔCt method with a two-fold expression difference (P < .05) as a cut-off level, although iron showed differential effects on most of the genes, IP3 R and PMCA genes were especially determined to have changed significantly. These results show that iron metabolism is an important metabolism due to changes in the expression of genes involved in calcium regulation and is a new perspective to overcome cancer/drug resistance.

Calcium homeostasis in cisplatin resistant epithelial ovarian cancer.

Intracellular calcium concentration ([Ca2+]i) may have an important role in the development of chemoresistance, which is an essential problem in cancer chemotherapy. Cisplatin (DDP), which modulates the intracellular calcium concentration by different mechanisms, is an antineoplastic agent with high success rate in cancer therapies. We investigated the regulatory role of [Ca2+] in cisplatin resistance in epithelial ovarian cancer cell line, in MDAH-2774, and its chemoresistant subclone MDAH-2774/DDP. The measurement of [Ca2+]i using fluorescence microscope, and flow cytometry revealed that the amount of intracellular calcium decreased in cisplatin resistant cells compared to the amounts in parental cells. mRNA expression profiles of calcium homeostasis-associated major genes (IP3R1/2/3, RYR1/2, SERCA1/2/3, NCX1/2/3, PMCA1/2/3, and PMCA4) decreased in cisplatin resistant cell line in comparison to the expression profiles in parental cells. Owing to the changes in the expression of genes involved in calcium regulation, these results show, drug resistance may be prevented by introducing a new perspective on the use of inhibitors and activators of these genes, and thus of cytostatic treatment strategies, due to changes in the expression of genes involved in calcium regulation.