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Anti-Tumor Effects of Ellagic Acid and Mesenchymal Stem Cell-Conditioned Medium on Breast Cancer Cells on the 3D Printed Pcl/Agarose Scaffolds Publisher



Ghaedamini S1 ; Kazemi M2, 3 ; Rabiei A1 ; Honarvar A4 ; Aliakbari M1 ; Karbasi S5
Authors
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Authors Affiliations
  1. 1. Department of Anatomical Sciences, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  2. 2. Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
  3. 3. Reproductive Sciences and Sexual Health Research Center, Isfahan University of Medical Sciences, Isfahan, Iran
  4. 4. Cellular and Molecular Research Center, Faculty of Medicine, Yasuj University of Medical Sciences, Yasuj, Iran
  5. 5. Department of Biomaterials, Nanotechnology and Tissue Engineering, School of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, Iran

Source: Journal of Drug Delivery Science and Technology Published:2024


Abstract

Numerous investigations have demonstrated that natural bioactive compounds, such as flavonoids, exhibit synergistic effects with anticancer agents utilized in clinical practice. Stem cell therapies play a critical role in the domain of oncology; nevertheless, conflicting results have surfaced regarding the potential pro-cancer or anti-cancer characteristics of mesenchymal stem cells. The primary aim of the current investigation was to examine the anticancer efficacy of ellagic acid (EA) alone or in combination with adipose tissue stem cells derived conditioned medium (ADSCs-CM) on human breast cancer cells. In order to overcome the potential effects of two-dimensional (2D) culture, a three-dimensional (3D) printed polycaprolactone (PCL)/agarose scaffold is utilized to evaluate cancer cell behavior. More recently it was reported this scaffold had open and interconnected pores, as well as good water absorption and mechanical properties. Assessment of MCF-7 cancer cell viability was conducted through MTT assay, flow cytometry, cell cycle assay, and quantitative real-time PCR within a 3D cell culture framework. The outcomes revealed a reduction in cancer cell viability across all treatment cohorts in comparison to the control group. Particularly noteworthy was the significantly enhanced effect of the EA and CM combination relative to each component administered individually. Flow cytometry assessment using annexin V/PI staining indicated a decrease in cancer cells, particularly evident in the combination-treated group. Furthermore, the mRNA expression levels of BAX, BCL2, vascular endothelial growth factor (VEGF), and caspase 3 genes were consistent with pathways associated with apoptosis. Consequently, the synergistic anti-proliferative impact of EA in conjunction with ADSCs-CM on MCF-7 cells has been substantiated. These findings have two important implications for breast cancer research; highlight the utility of the PCL/agarose scaffold as a cancer model and suggest new avenues for the development of adjuvant anticancer therapeutic approaches. © 2024 Elsevier B.V.
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