Abstract
Purpose
Sarcomas are rare and heterogenic tumors with unclear etiology. They develop in bone and connective tissue, mainly in pediatric patients. To increase efficacy of current therapeutic options, natural products showing selective toxicity to tumor cells are extensively investigated. Here, we evaluated antitumor activity of bacterial pigment violacein in osteosarcoma (OS) and rhabdomyosarcoma (RMS) cell lines.
Methods
The toxicity of violacein was assessed in vitro and in vivo, using MTT assay and FET test. The effect of violacein on cell migration was monitored by wound healing assay, cell death by flow cytometry, uptake of violacein by fluorescence microscopy, generation of reactive oxygen species (ROS) by DCFH-DA assay and lipid peroxidation by TBARS assay.
Results
Violacein IC50 values for OS and RMS cells were in a range from 0.35 to 0.88 µM. Its selectivity toward malignant phenotype was confirmed on non-cancer V79-4 cells, and it was safe in vivo, for zebrafish embryos in doses up to 1 µM. Violacein induced apoptosis and affected the migratory potential of OS and RMS cells. It was found on the surfaces of tested cells. Regarding the mechanism of action, violacein acted on OS and RMS cells independently of oxidative signaling, as judged by no increase in intracellular ROS generation and no lipid peroxidation.
Conclusion
Our study provided further evidence that reinforces the potential of violacein as an anticancer agent and candidate to consider for improvement of the effectiveness of traditional OS and RMS therapies.
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Data availability
The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.
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Funding
This work was supported by the Ministry of Education, Science and Technological Development of the Republic of Serbia (project numbers 173008, 451–03-68/2020–14/200042, 451–03-9/2021–14/200042, 451–03-68/2022–14/200042).
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Conceptualization: SK and JJ; methodology and investigation: EM, NS, SB, NS, AB, VC and JJ; formal analysis: EM, NS, MN and JJ; resources: AB, VC and SK; visualization: EM and JJ; supervision: JJ and SK; writing—original draft: JJ and SK; writing—review and editing: EM, MN and VC; project administration and funding acquisition: SK. All authors have read and agreed to the submitted version of the manuscript.
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Milosevic, E., Stanisavljevic, N., Boskovic, S. et al. Antitumor activity of natural pigment violacein against osteosarcoma and rhabdomyosarcoma cell lines. J Cancer Res Clin Oncol 149, 10975–10987 (2023). https://doi.org/10.1007/s00432-023-04930-9
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DOI: https://doi.org/10.1007/s00432-023-04930-9