title: Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53.
abstract: Osteosarcoma is the most common bone cancer. Although the emergence of multidrug therapies has improved available treatments for osteosarcoma, approximately 30% of patients will still develop metastasis. Currently, much anticancer therapy uses drugs that affect oncogenes/tumor suppressor genes, such as p53 (up-regulation) and Sp1 (down-regulation). Chalcones are secondary metabolites of plants and have been demonstrated to induce apoptosis in human cancer cells. Building on this knowledge, we evaluated the ability of trans-chalcone to reduce viability, to induce apoptosis, and to alter gene expression of p53 and Sp1 in human osteosarcoma cell lines. We found that treatment of trans-chalcone inhibited growth of osteosarcoma cells in a dose- and time-dependent manner, with significant inhibition at 10 μM after 48 h; apoptosis was also induced in a dose-dependent manner, with 1.9- and 3.6-fold induction at 10 μM and 50 μM, respectively, compared to non-treated 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. trans-chalcone and its derivatives could be important in the development of future clinical trials in osteosarcoma. © 2015 Wiley Periodicals, Inc.
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.|Biotechnology Unit, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
authors: Gabriel
authors: G
authors: Silva
authors: Biotechnology Unit, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil. marins@gmb.bio.br.
authors: Mozart
authors: M
authors: Marins
authors: Biotechnology Unit, University of Ribeirão Preto, Ribeirão Preto, São Paulo, Brazil.
authors: Ana Lúcia
authors: AL
authors: Fachin
authors: Department of Nutrition and Food Science, College of Agriculture and Natural Resources, University of Maryland, College Park, Maryland.
authors: Seong-Ho
authors: SH
authors: Lee
authors: Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee. sbaek2@utk.edu.
authors: Seung Joon
authors: SJ
authors: Baek
mesh_terms: D000072283:A549 Cells; D001859:Bone Neoplasms / Q000188:drug therapy / Q000235:genetics*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002599:Chalcone / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D045325:HCT116 Cells; D006801:Humans; D012516:Osteosarcoma / Q000188:drug therapy / Q000235:genetics*; D016329:Sp1 Transcription Factor / Q000235:genetics* / Q000378:metabolism; D016159:Tumor Suppressor Protein p53 / Q000235:genetics* / Q000378:metabolism; D015854:Up-Regulation
chemical_list: D016329:Sp1 Transcription Factor; C108209:SP1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D002599:Chalcone
keywords: Sp1; chalcone; osteosarcoma; p53; transcriptional regulation