The effects of terbium on the accumulation of cisplatin in human ovarian cancer cells

Abstract

In this investigation, we report a relationship between the terbium (Tb3+) binding protein and the accumulation of cisplatin in human ovarian cancer cells. The number of Tb3+ binding sites in cisplatin-resistant C13+ cells is significantly greater by 79% than those in cisplatin-sensitive 2008 cells. Exposure to Tb3+ also increased the cellular accumulation of cisplatin. The accumulation of cisplatin as a function of the Tb3+ concentration in the C13+ cells (0.85%/microM Tb3+) was significantly greater than the accumulation of cisplatin in 2008 cells with respect to Tb3+ (0.46%/microM Tb3+). The number of Tb3+ binding sites in revertant RH4 cells was similar to that in 2008 cells. The RH4 cells were less sensitive to the stimulatory effects of Tb3+ than the C13+ cells. Our results show that the Tb3+ binding protein correlates with cisplatin resistance, and the receptor binding of Tb3+ increases the accumulation of cisplatin in cisplatin-resistant cells.

Inhibition of thioredoxin reductase by lanthanum chloride

“…However, the binding of lanthanum ions to the membrane increases membrane permeability hence facilitating the passage of other lanthanum ions [61]. It was further reported that other lanthanides such as gadolinium ion could form pores in erythrocyte membranes [62] while terbium is able to bind to membranes of ovarian cancer cells increasing the accumulation of cisplatin in cisplatinresistant cancer cells [63]. Transport of lanthanum is enhanced by complexation with various ligands, forming species able to diffuse through the plasma membrane and to enter the cell more easily than lanthanum ion.…”

Lanthanides as Anticancer Agents

“…Recently, fifteen newly synthesized cerium(III), lanthanum(III) and neodymium(III) complexes with bis-coumarins (13)(14)(15)(16)(17) were characterized, and their cytotoxic activities were tested on a variety of cancer cell lines [46,[49][50]. Significant difference in activity was found.…”

“…However, the clinical success will depend on whether the opposing effects can be modulated. To this end, it is essential to understand the nature of the duality [14].…”

“…The lanthanide complexes were generally more cytotoxic than the corresponding lanthanide salts or ligands against investigated cell lines. Complexes of neodymium (III) with bis-coumarins: 3,3' -benzylidene -bis ( 4 -hydroxy -2H -1 -benzopyran -2 -one ) (13); bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-2-ylmethane (14); bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-3-yl-methane (15); bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-piridin-4-yl-methane (16); and bis(4-hydroxy-2-oxo-2H-chromen-3-yl)-(1H-pyrazol-3-yl)-methane (17) were synthesized and cytotoxic screening by MTT assay was carried out [49]. The complexes were tested on HL-60, HL-60/Dox and SKW-3 cell lines.…”