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Anti-cancer activity of trans-chalcone in osteosarcoma: Involvement of Sp1 and p53
Gabriel Silva1,2, Mozart Marins3, Ana Lúcia Fachin2
1Department of Biomedical and Diagnostic Sciences, College of Veterinary Medicine, University of Tennessee, Knoxville, Tennessee.
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.
Insights
Trans-chalcone effectively inhibits osteosarcoma cell growth and induces apoptosis. This natural compound impacts key cancer genes, Sp1 and p53, offering potential for new bone cancer treatments.
Area of Science:
- Oncology
- Pharmacology
- Biochemistry
Background:
- Osteosarcoma is the most common primary bone cancer.
- Despite advances, ~30% of patients experience metastasis.
- Current therapies target oncogenes/tumor suppressor genes like p53 and Sp1.
Purpose of the Study:
- To evaluate trans-chalcone's effect on osteosarcoma cell viability and apoptosis.
- To investigate trans-chalcone's impact on p53 and Sp1 gene expression.
- To explore trans-chalcone as a potential therapeutic agent for osteosarcoma.
Main Methods:
- Human osteosarcoma cell lines were treated with varying concentrations of trans-chalcone.
- Cell viability and apoptosis induction were measured.
- Gene expression levels of p53 and Sp1 were analyzed at transcriptional and post-translational levels.
Main Results:
- Trans-chalcone significantly inhibited osteosarcoma cell growth in a dose- and time-dependent manner (e.g., 10 μM at 48h).
- Apoptosis was dose-dependently induced by trans-chalcone (1.9-fold at 10 μM, 3.6-fold at 50 μM).
- Trans-chalcone downregulated Sp1 transcriptionally and upregulated p53 post-translationally.
Conclusions:
- Trans-chalcone demonstrates potent anti-cancer activity against osteosarcoma cells.
- The compound modulates key regulatory genes (Sp1, p53), suggesting a novel mechanism of action.
- Trans-chalcone and its derivatives hold promise for future osteosarcoma clinical trials.
