Metastasis is the primary cause of death in cancer patients. Many current chemotherapeutic
agents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumor
size, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novel
anticancer compounds with both effects need to be developed. In this work, we analyze the antimetastatic properties of prodigiosin and obatoclax (GX15-070), anticancer drugs of the Prodiginines
(PGs) family. We studied PGs’ effects on cellular adhesion and morphology in the human primary
and metastatic melanoma cell lines, SK-MEL-28 and SK-MEL-5, and in the murine melanoma cell
line, B16F10A. Cell adhesion sharply decreased in the treated cells, and this was accompanied by a
reduction in filopodia protrusions and a significant decrease in the number of focal-adhesion structures. Moreover, cell migration was assessed through the wound-healing assay and cell motility was
severely inhibited after 24 h of treatment. To elucidate the molecular mechanisms involved, changes
in metastasis-related genes were analyzed through a gene-expression array. Key genes related to
cellular invasion, migration and chemoresistance were significantly down-regulated. Finally, an
in vivo model of melanoma-induced lung metastasis was established and significant differences in
lung tumors were observed in the obatoclax-treated mice. Altogether, these results describe, in depth,
PGs’ cellular antimetastatic effects and identify in vivo antimetastatic properties of Obatoclax.
