Abstract 4654: Antitumorigenic activity of trans-chalcone in osteosarcoma

Abstract

Abstract Background and Aims: Osteosarcoma is the most common bone cancer, and it affects mostly teenagers and children. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Thus, there is a clear need to identify new anticancer therapies. Currently, much anticancer therapy uses drugs that affect molecular targets, such as up-regulation of p53 and down-regulation of Sp1. Building on this knowledge, our aims in this work were to evaluate the ability of trans-Chalcone to reduce viability, induce apoptosis, and to alter the levels of p53 and Sp1 in human osteosarcoma cell lines. Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Methods: Osteosarcoma cell viability and apoptosis were evaluated by MTT assay and flow cytometry, respectively. The expression of p53 and sp1 was assessed by Western blotting. Transcriptional and post-translational regulation were measured by luciferase assay and proteasomal inhibitor experiments. Results: We identified that cell growth was inhibited by trans-Chalcone in a dose- and time-dependent manner, with a significant inhibition at 10 μM after 48 hours. After 24 hours of treatment with trans-Chalcone, apoptosis was induced in a dose-dependent manner-fold induction at 1.9 and 3.6 at 10 μM and 50 μM, respectively, compared to control. Western blot analysis indicated that trans-chalcone reduced Sp1 and induced p53 expression, compared to control cells. Further experiments suggest that trans-Chalcone affected Sp1 down-regulation at the transcriptional level, whereas trans-chalcone up-regulated p53 expression at the post-translational level. These results were confirmed by a luciferase assay of the MDM2 promoter and a proteasomal degradation assay using several inhibitors. Conclusions: Trans-Chalcone inhibits cell growth and induces apoptosis in osteosarcoma cells and targets p53 tumor suppressor and Sp1 oncogenic proteins in osteosarcoma. Thus, trans-chalcone could be the focus of future clinical trials to develop an anti-cancer drug for osteosarcoma patients. Support: The University of Tennessee Center of Excellence in Livestock Diseases and Human Health and a grant (No. process: BEX 3159/14-0) from the CAPES Foundation, an agency under the Ministry of Education of Brazil. Citation Format: Gabriel da Silva, Mozart Marins, Ana Lúcia Fachin, Seung J. Baek. Antitumorigenic activity of trans-chalcone in osteosarcoma. [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 4654. doi:10.1158/1538-7445.AM2015-4654