RT info:eu-repo/semantics/article
T1 Antimetastatic Properties of Prodigiosin and the BH3-Mimetic Obatoclax (GX15-070) in Melanoma
A1 Espona Fiedler, Margarita
A1 Manuel Manresa, Pilar
A1 Benítez-García, Cristina
A1 Fontova Pale, Pere
A1 Quesada Pato, Roberto
A1 Soto Cerrato, Vanessa
A1 Pérez Tomás, Ricardo
K1 Metastasis
K1 Obatoclax
K1 Prodigiosin
K1 Prodiginines
K1 BH3-mimetic
K1 Melanoma
K1 Migration
K1 Química orgánica
K1 Chemistry, Organic
K1 Salud
K1 Health
K1 Medicina
K1 Medicine
AB Metastasis is the primary cause of death in cancer patients. Many current chemotherapeuticagents only show cytotoxic, but not antimetastatic properties. This leads to a reduction in tumorsize, but allows cancer cells to disseminate, which ultimately causes patient death. Therefore, novelanticancer 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 primaryand metastatic melanoma cell lines, SK-MEL-28 and SK-MEL-5, and in the murine melanoma cellline, B16F10A. Cell adhesion sharply decreased in the treated cells, and this was accompanied by areduction 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 wasseverely inhibited after 24 h of treatment. To elucidate the molecular mechanisms involved, changesin metastasis-related genes were analyzed through a gene-expression array. Key genes related tocellular invasion, migration and chemoresistance were significantly down-regulated. Finally, anin vivo model of melanoma-induced lung metastasis was established and significant differences inlung 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.
PB MDPI
YR 2022
FD 2022-12
LK http://hdl.handle.net/10259/7559
UL http://hdl.handle.net/10259/7559
LA eng
NO This research has been funded by Instituto de Salud Carlos III (Grants PI18/00441; FIS PI10/00338) (Co-funded by European Regional Development Fund. ERDF, a way to build Europe).
DS Repositorio Institucional de la Universidad de Burgos
RD 24-nov-2024