Abstract 4550: Antiproliferative activity of 8-methoxypsoralen without UV light irradiation: A new perspective for cancer therapy

Abstract

The furanocoumarin-derivative 8-methoxypsoralen (8-MOP) is commonly used combined with UV light irradiation for treatment of skin diseases. We have recently demonstrated that 8-MOP inhibits GST-P1 in tumor cells and acts as chemosensitizer. These new data show direct antitumor activity of this compound without photoactivation in an in vitro model of glioma, the most common and lethal primary malignant brain tumor. Rat glioma C6 cells and human glioblastoma GL-15 cells were submitted to treatment with 8-MOP, as well as primary rat astrocytes cultures for comparison. Cell viability was measured by MTT assay; phase contrast microscopy and quantification of total protein content were also performed. The trypan blue dye exclusion assay and colony formation test were used to analyze cell proliferation. Flow cytometry was used for cell cycle analyses. Morphological changes were accessed by electron microscopy and proteins expression was studied by using immunolabeling techniques. As main results, 8-MOP reduced cell viability and cellularity, time- and dose-dependently, more efficiently in tumor than in normal cells. The compound also showed considerable antiproliferative effect against tumor cells and induced cell death by apoptosis when used at high concentration. However, 8-MOP did not promote cell cycle arrest and also did not increase labeling of markers associated to bad prognostic. Additional tests with cell lines from other tumors (breast cancer, colorectal cancer and lymphoma) showed that they respond differently to 8-MOP treatment, pointing to a pathway-specificity of its action. A qualitative structure-activity relationship study was also performed using coumarin derivatives structurally related to 8-MOP, from these experiments it was possible to suggest the relevance of each part of 8-MOP molecular structure for antiproliferative action. These results point furanocoumarin derivatives as a possible new class of anticancer agents. Note: This abstract was not presented at the meeting. Citation Format: Diêgo M. de Oliveira, Rute M F Lima, Eudes S. Velozo, Ilza A. Amorim, Tales H A Mota, Silvia L. Costa, Fabio P. Silva, Ramon S. El-Bachá. Antiproliferative activity of 8-methoxypsoralen without UV light irradiation: A new perspective for cancer therapy. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 4550. doi:10.1158/1538-7445.AM2015-4550