CONICET | Buscador de Institutos y Recursos Humanos

HSPB1 (HSP27) is a heat shock protein strongly related to cancer; this protein participates in many events associated with tumor progression and resistance to anticancer treatments. Our laboratory is exploring ways to interfere with the HSPB1 response testing phytochemicals selected from autochthonous plants grown in the semi desert area of Mendoza and San Luis. The study involves breast cancer, cervical cancer and glioma cells exposed to 3-isopropyl-4-methyl-5,7-dihydroxycoumarin (C13), a semi-synthetic coumarin previously characterized with inhibitory activity of replicative process that could be considered an attractive target in cancer studies. We have previously shown the anti-tumoral activity of C13. Moreover, this study has demonstrated the anti-proliferative effects on cancer cell lines by decreasing proliferation as measured by Ki67. Senescence-associated-β-galactosidase (SA-β-gal) staining was performed and cellular senescence was significantly induced in treated cells. To further investigate the biological mechanisms we have analyzed HSPB1, PTEN and β-catenin expression and localization by Western Blot and immunofluorescence techniques. PTEN is a tumor suppressor with tyrosine phosphatase activity that negatively regulates the PI3K/PKB/AKT pathway. On the other hand, β-catenin participates in cell-cell adhesion complexes and also has downstream signaling functions in the WNT /Wingless pathway. C13 induced significant changes in HSPB1 total content also in phosphorylation protein status, with changes in cellular localization. β-catenin and PTEN have shown an important re-localization according to drug concentration in cervical cancer (HeLa) and glioma cells (Gli36). The expression of both proteins has been modulated by C13 treatment. These results suggest that studied proteins related to carcinogenesis and tumor progression could be essential in the mechanism of action of the natural compound