Controversial effect on Erk activation of some cytotoxic drugs in human LOVO colon cancer cells.

UNLABELLED: The use of some classic antibiotics was recently shown to inhibit growth and to induce apoptosis in human LOVO colon cancer cells. In this study, we describe that ciprofloxacin (CI), trimebutine maleate (COL) and tiemonium methylsulfate (VIS) greatly inhibit cell proliferation in vitro. Proliferation inhibition reached its maximum at 10(-4 )M, 10(-3 )M and 10(-2 )M, respectively, for COL, CI and VIS. Moreover, phospho-extracellular-regulated kinase was totally abrogated in non-apoptotic cytotoxicity of VIS but decreases or increases in the apoptotic inhibition, respectively, of COL and CI treatments. ABBREVIATIONS: CI: ciprofloxacin; COL: trimebutine maleate; VIS: tiemonium methylsulfate; MAPK/Erk: mitogen-activated protein kinases/extracellular-regulated kinase.

Effect of estradiol and clomiphene citrate on Erk activation in breast cancer cells.

The mitogen-activated protein kinase (MAPK) signaling pathway plays key roles in the transmission of proliferative signals in normal and dysregulated cells. Nevertheless, some studies have shown that activation of the extracellular regulated kinases 1/2 (Erk1/2) is involved in apoptosis. In this study, we evaluate the effect of two fertilizing drugs, clomiphene citrate and estradiol, on the activation of Erk1/2 and the viability of two breast cancer cell lines, MCF-7 (hormone dependent) and BT20 (hormone independent).We show that both drugs induce Erk1/2 phosphorylation in MCF-7 and BT20 cells despite their opposite effect on cell viability. In fact, clomiphene citrate is significantly proapoptotic while estradiol promotes cell proliferation. The fact that phospho-Erk1/2 is a common element to both mechanisms suggests that specific factors deciding between proliferation and apoptosis must be operative downstream of this signaling pathway.