Magnesium concentration in cisplatin-sensitive and -resistant human ovarian cancer cell lines: preliminary results

Among the mechanisms responsible for cisplatin (cDDP)-resistance, the higher plasma and mitochondrial membrane potential is central for the resistant phenotype [1] in a cDDP-resistant human ovarian cancer cell line (C13*) in comparison to its -sensitive parental line (2008). Since mitochondrial membrane potential Dym has been shown to be also involved in the homeostasis of intracellular magnesium concentration [2], we hypothesized that modifications of Mg2+ concentrations ([Mg]) and of their sub-cellular distribution, might be involved in the occurrence of cDDP- resistance. ICP, AA and fluorescence studies revealed a higher total [Mg] in C13* than in 2008 cells with a ratio [Mg]C13/[Mg]2008=1.3. RH4 cells (reverted from C13* cells by exposure to the lipophilic cationic mitochondrial poison rhodamine 123) showed a [Mg] as well as Dym and sensitivity to cDDP intermediate between the two cell lines. On the contrary, another couple of cDDP-sensitive and –resistant human ovarian cancer cell lines (A2780 and A2780-CP) showed a ratio of 0.8 which might be the consequence of the lower mitochondrial mass in the resistant cells, compared to the sensitive ones [3]. In addition, we noticed a cDDP dose-dependent increase of [Mg] in 2008 cells but not in C13* cells after 72 h-treatment; whereas the exposure to compounds that inhibit cell growth also by affecting mitochondrial functionality caused a concentration-dependent decrease of [Mg] in both lines [4]. All together, these preliminary studies suggest a causal relationship between total intracellular [Mg] and mitochondrial alterations raised during the selection of cDDP-resistance phenotype