Tl(I) AND Tl(III) prevent PC12ADH cell proliferation

SALVATIERRA FRÉCHOU DM, POTAP MD, SCHWARZBAUM PJ, VERSTRAETEN SV. TL(I) AND TL(III) PREVENT PC12ADH CELL PROLIFERATION

Simposio; Reunión Conjunta de Sociedades de Biociencias; 2017

Thallium (Tl) induces apoptosis in PC12 cells. However, in a PC12cell adherent variant (PC12adh), this effect was not observed, althougha potential cytotoxic effect of Tl on this cell line could not bediscarded.MTT reduction, evaluated in PC12adh cells incubated in thepresence of 10-100 μM Tl(I) or Tl(III) (24-72 h), was significantlydecreased after 24 h of cell exposure. Tl did not cause cell necrosis,as evaluated from LDH release or nuclear staining with acridineorange and ethidium bromide. To evaluate if Tl could alter PC12adhcell proliferation, the number of cells was estimated by Trypan bluestaining. In control samples, the number of cells increased linearlywith time. In contrast, in 100 μM Tl-treated samples the amounts ofcells remained constant after 48 h of exposure, and were markedlylower than those of the controls (two-way ANOVA). By using specificinhibitors, we observed that Tl did not affect ERK-, mTOR-, PLC-,PKC-, and p53-dependent proliferative pathways. In contrast, inhibitionof PI3K enhanced Tl-dependent prevention of cell proliferation,suggesting that this pathway could partially counteract the effectsof Tl. Cell cycle analysis by flow cytometry indicated that both Tl(I)and Tl(III) caused partial arrest of the cycle in G2/M phase, withoutaffecting S phase. Accordingly, the amounts of cells in G0/G1 phasedecreased with the time of exposure to Tl. Cell volume (forwardscatter) and internal complexity (side scatter) also increased withtime, in accordance with the appearance of intracellular vacuoles. Tldid not cause cell senescence, indicated by the lack of activation ofsenescence-associated β-galactosidase. Together, present resultssuggest that both Tl(I) and Tl(III) prevent PC12adh cell proliferation,and the signaling pathways affected by these cations remain to beelucidated.Keywords: thallium, cell proliferation, cytotoxicity, cell cycle