Aim: 

The cytotoxicity of a new Pt complex, [Pt(O,O'-acac)(g-acac)(DMS)] (Pt-2acac), has been tested in both HeLa cervical cancer cells [1] and MCF-7 breast cancer cells [2]. Here, we used both normal and cancerous human breast cells in primary culture in order to test and compare the cytotoxic effects of Pt-2acac.

Methods: 

Primary cultures from five invasive intraductal breast cancer tissues and the corresponding histologically proven non-malignant tissue adjacent to the tumour were obtained as previously described [3], and used at passages two to three.

Cells were treated with various concentrations of Pt-2acac, and viable cell number was determined 24, 48 and 72 h later by MTT colorimetrical assay. ERK1/2 phosphorylation was assessed by western blotting.

Results: 

Treatment of human epithelial breast cells with Pt-2acac induced cell death. Tumor cells were significantly more sensitive than normal cells; for example, 50% of cancerous and normal cells treated with 100 mM Pt-2acac died after 24 and 72 h, respectively. Pt-2acac treatment provoked ERK phosphorylation in both normal and cancerous cells. The cytotoxic effects of Pt-2acac decreased when normal cells were pre-incubated with the MEK inhibitor PD98059, while in tumor cells it had no effects.

Conclusions: 

Pt-2acac has higher cytotoxicity in epithelial breast cancer cells than in normal cells in primary culture. Furthermore, ERK appears to have a pro-apoptotic effect only in normal cells treated with Pt-2acac.

References: 

[1] Muscella A et al. Biochem Pharmacol. 2007,74:28–40. [2] Muscella A et al. Br J Pharmacol 2008,153:34–49 [3] Greco S et al. Cell Calcium 2002, 32:1–10