Pomegranate seed extract enhances the inhibitory effect of adipose-derived mesenchymal stem cells on breast cancer cell line in co-culture conditions

Nahid Moradi-Gharibvand; Mohsen Setayeshmehr; Mohammad Kazemi; Azadeh Safaee; Laya Sadat Khorsandi; Darioush Bijan Nejad; Seyed Javad Hasheminia; Batool Hashemibeni

doi:10.4103/1735-5362.350238

Pomegranate seed extract enhances the inhibitory effect of adipose-derived mesenchymal stem cells on breast cancer cell line in co-culture conditions

Res Pharm Sci. 2022 Jul 14;17(4):372-382. doi: 10.4103/1735-5362.350238. eCollection 2022 Aug.

Authors

Nahid Moradi-Gharibvand¹, Mohsen Setayeshmehr², Mohammad Kazemi³, Azadeh Safaee¹, Laya Sadat Khorsandi⁴, Darioush Bijan Nejad⁵, Seyed Javad Hasheminia⁶, Batool Hashemibeni¹

Affiliations

¹ Department of Anatomical Sciences and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
² Department of Biomaterials, Nanotechnology, and Tissue Engineering, Faculty of Advanced Technologies in Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
³ Department of Genetics and Molecular Biology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.
⁴ Cellular and Molecular Research Center, Medical Basic Sciences Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.
⁵ Department of Anatomical Sciences, Faculty of Medicine, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, I.R. Iran.
⁶ Department of Immunology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, I.R. Iran.

Abstract

Background and purpose: Pomegranate seed extract (PSE) possesses anticancer activities and healing effects. Adipose-derived stem cells (ADSCs) are being considered a new candidate for cancer treatment. The purpose of this study was to investigate the effect of PSE on the cell cycle and apoptosis of the MCF-7 cell line in the co-culture condition with ADSCs.

Experimental approach: MCF-7 and ADSC cells (ratio 1/1) were cultured in a transwell plate with and without PSE (PSE-co-culture and co-culture groups). MCF-7 cells were cultured in monolayer without and with PSE (mono-culture and PSE-mono-culture groups). MCF-7 cell line was harvested on day 5 and cell viability, apoptotic activity, cell cycle, and gene expression were evaluated.

Findings / results: The results of the MTT assay indicated that PSE at 100 μg/mL has the highest cytotoxicity on the MCF-7 in the PSE-co-culture group. The cell cycle analysis revealed that ADSCs in combination with PSE significantly increased the population of MCF-7 cells in the G1 phase, resulting in the arrest of MCF-7 cells cycle in the G0/G1 transition. In addition, the most apoptotic MCF-7 cells (41.5%) were detected in the same group. Expression of BAX and caspase3 genes were upregulated while anti-apoptotic (BCL-2) and angiogenesis inducer (VEGF) genes were downregulated in the PSE-co-culture group compared with the other groups.

Conclusion and implications: ADSCs reduced cell viability and proliferation of MCF-7 cells in co-culture conditions and adding PSE to the medium increased the apoptosis of cancer cells. This study suggests that ADSCs with PSE can suppress tumor cells.

Keywords: Adipose-derived stem cells; Apoptosis; Breast cancer; Cell cycle; Co-culture; Pomegranate seed extract.