Tl(I) AND Tl(III) PREVENT PC12ADH CELL PROLIFERATION

SALVATIERRA FRÉCHOU, D. M.; VERSTRAETEN, S. V.; SCHWARZBAUM, P. J.; POTAP, M.

Buenos Aires

Congreso; REUNIÓN CONJUNTA DE SOCIEDADES DE BIOCIENCIAS; 2017

Sociedades de Biociencias

Thallium (Tl) induces apoptosis in PC12 cells. However, in a PC12 cell adherent variant (PC12adh), this effect was not observed, although a potential cytotoxic effect of Tl on this cell line could not be discarded. MTT reduction, evaluated in PC12adh cells incubated in thepresence of 10-100 µM Tl(I) or Tl(III) (24-72 h), was signifcantly decreased after 24 h of cell exposure. Tl did not cause cell necrosis, as evaluated from LDH release or nuclear staining with acridine orange and ethidium bromide. To evaluate if Tl could alter PC12adh cell proliferation, the number of cells was estimated by Trypan blue staining. In control samples, the number of cells increased linearly with time. In contrast, in 100 µM Tl-treated samples the amounts of cells remained constant after 48 h of exposure, and were markedlylower than those of the controls (two-way ANOVA). By using specifc inhibitors, we observed that Tl did not affect ERK-, mTOR-, PLC-, PKC-, and p53-dependent proliferative pathways. In contrast, inhibition of PI3K enhanced Tl-dependent prevention of cell proliferation, suggesting that this pathway could partially counteract the effects of 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, without affecting S phase. Accordingly, the amounts of cells in G0/G1 phase decreased with the time of exposure to Tl. Cell volume (forward scatter) and internal complexity (side scatter) also increased with time, in accordance with the appearance of intracellular vacuoles. Tl did not cause cell senescence, indicated by the lack of activation of senescence-associated β-galactosidase. Together, present results suggest that both Tl(I) and Tl(III) prevent PC12adh cell proliferation, and the signaling pathways affected by these cations remain to be elucidated.