Antitumoral activity of 3-isopropyl-4-methyl-5,7-dihydroxycoumarin and its action mechanism associated to HSPB1: Preliminary Results

Abstract

Our laboratory has been involved in the study of HSPB1 (HSP27) in cancer; this protein participates in many events related with cancer progression and resistance to anticancer treatments. We are now 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. The HSPB1 response has been examined by immunocytochemistry, the cytotoxic effect was studied by the MTT assay and the effect on the cell migration by the wound healing assay. Cell death was evaluated by flow cytometry and immunocytochemistry. C13 induced significant changes in HSPB1 total content and in phosphorylation protein status, with changes in cellular localization. The survival of the cancer cells was significantly decreased according to drug concentration and time of exposure. Cell migration decreased and cell death by apoptosis increased in treated cells. Aggresome structures were observed as a distinctive cytotoxic effect on Gli36 cells.