Ponente
Descripción
Sticholysin II (StII) is a pore-forming protein derived from the sea anemone Stichodactyla helianthus[1]. Due to the high cytolytic activity of StII, several projects are being developed in our laboratory for its application in anti-tumor strategies. However, its use to generate combined antitumor treatments has not been widely explored. Thus, the aim of this work was to evaluate the cytotoxic effect of combining StII with the chemotherapeutic agents mitomycin C and oxaliplatin, on A549 (human non-small cell lung adenocarcinoma), CT26 (murine colon carcinoma) and MB16.F10 (murine melanoma) cell lines by the MTT assay. The cytotoxic activity of StII was found in the nanomolar concentration range for all cell lines, while for mitomycin C and oxaliplatin it was found in the micromolar range. Low doses of mitomycin C and oxaliplatin induced more effective cytotoxicity when combined with StII, in what appears to be an additive or synergistic effect. In vitro studies in CT26 cells with the ABC family transporter P-glycoprotein (Gp-P), which has been found to be responsible, at least in part, for the drug resistance phenotype [2] revealed that StII decreased the activity of this transporter. This reduced activity may underlie the enhanced efficacy of the chemotherapeutics studied when combined with StII. Therefore, StII could be used to increase the efficacy of conventional chemotherapeutic drugs, either by facilitating their entry into the cell and/or by reducing undesirable Gp-P activity. These results constitute the first evidence of a possible cytotoxicity-enhancing effect of chemotherapeutic agents when combined with StII.
