2-((3-(2-3-dichlorophenoxy)propyl)amino)ethanol and Ovarian-Neoplasms

Emergence of chemoresistance in the course of treatments with platinum drugs remains a major hurdle to ovarian carcinoma therapy. We have previously shown that acquisition of cisplatin resistance by OAW42-R ovarian carcinoma cells was associated with the loss of ERK activation in response to cisplatin. To try to sensitize this cell line by restoring ERK activation, we tested a new synthetic compound, 2[[3-(2,3-dichlorophenoxy)propyl]amino]ethanol (2,3-DCPE), which was described to induce ERK activation and to display anticancer properties.. We treated four ovarian carcinoma cell lines with 2,3-DCPE, alone or combined with cisplatin. We characterized its effects on apoptosis induction and proliferation and correlated them with molecular modulations.. We showed that 2,3-DCPE induced cell death and ERK phosphorylation in a time- and concentration-dependent manner in OAW42-R cells. 2,3-DCPE-triggered apoptosis was also associated with the inhibition of Bcl-2 expression and, to a less extent, with that of Bcl-xL. Treatment with 2,3-DCPE also elicited a strong G0/G1 cell cycle arrest, accompanied with p21WAF1/CIP1 up-regulation. All of these effects revealed to be irreversible. Moreover, 2,3-DCPE exerted a cytostatic effect on OAW42, IGROV1-R10 and SKOV3 ovarian carcinoma cells, the sensitivity to 2,3-DCPE appearing in particular linked with a low basal level of P-ERK. Finally, we showed that 2,3-DCPE increased the cytotoxic effect of cisplatin in OAW42-R resistant cells.. Our results emphasized the potential interest of 2,3-DCPE, used alone or combined with cisplatin, for ovarian carcinoma treatment. The absence of basal P-ERK may constitute a predictive marker of response to this novel therapy.

Topics: Antineoplastic Combined Chemotherapy Protocols; Apoptosis; bcl-X Protein; Cell Line, Tumor; Chlorobenzenes; Cisplatin; Cyclin-Dependent Kinase Inhibitor p21; Drug Synergism; Enzyme Activation; Ethanolamines; Extracellular Signal-Regulated MAP Kinases; Female; G1 Phase; Humans; Ovarian Neoplasms; Phosphorylation; Proto-Oncogene Proteins c-bcl-2; Resting Phase, Cell Cycle