# Sex‐Dependent Paracrine Effect of Conditioned Media From Adipose Tissue Derived Mesenchymal Stem Cells on Prostate Cancer Cells

**Authors:** Akram Mirzaei, Rahil Mashhadi, Ziba Aghsaeifard, Mehrnaz Izadi, Seyedeh Negin Hashemi Dougaheh, Reza Omid, Fateme Guitynavard, Parsa Nikoofar, Seyed Mohammad Kazem Aghamir

PMC · DOI: 10.1111/jcmm.70569 · Journal of Cellular and Molecular Medicine · 2025-05-12

## TL;DR

This study shows that male-derived stem cell media better reduce prostate cancer cell growth and aggression compared to female-derived media.

## Contribution

The novel finding is that the sex of the stem cell donor affects the anti-cancer properties of conditioned media in prostate cancer.

## Key findings

- Male MSC conditioned media (MCM) reduced N-Cadherin, Vimentin, EGFR, and BCL2 gene expression more than female MSC media.
- MCM increased BAX and E-Cadherin gene expression in PC3 cells, indicating enhanced apoptosis and reduced cancer aggression.
- MCM was more effective in inhibiting epithelial-mesenchymal transition and cancer cell survival pathways.

## Abstract

Considering the different behaviour of cells in response to diseases in different conditions and sex hormone‐dependent cancers, we addressed the possible effect of the sex of the source of these cells from adipose tissue on prostate cancer cells. In this in vitro study, we evaluated the effects of male and female MSC Conditioned Media (MCM, FCM) on prostate cancer cells. The assessment included Hoechst dye staining, a scratch‐wound assay, a colony formation assay, and a flow cytometric analysis of apoptosis and the cell cycle. We also performed real‐time PCR to examine various genes, including apoptosis‐related genes, epithelial‐mesenchymal transition (EMT) genes, angiogenesis‐related genes, and cell growth and survival biomarkers. Our results indicated that the IC50 values were 50% and 75% media in MCM and FCM in each of the three prostate cancer cell lines, respectively. An evaluation of gene expression revealed that in all three prostate cancer cell lines, treatment with MCM was more effective than FCM in reducing the expression of N‐Cadherin and Vimentin, EGFR and BCL2 genes (p < 0.001). Furthermore, the MCM significantly increased the expression of BAX and E‐Cadherin genes (p < 0.001) in the PC3 cell line. MCM proved to be more effective than FCM in reducing the expression of the epithelial‐mesenchymal transition pathway, EGFR gene, and Apoptosis Regulator (BCL2) in the PC3 cell line. Due to its potential in regenerative medicine and cell therapy, this approach may serve as an effective treatment option for advanced prostate cancer.

## Linked entities

- **Genes:** CadN (Cadherin-N) [NCBI Gene 35070], PRELID1 (PRELI domain containing 1) [NCBI Gene 737446], EGFR (epidermal growth factor receptor) [NCBI Gene 1956], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596], BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581], shg (shotgun) [NCBI Gene 37386]
- **Diseases:** prostate cancer (MONDO:0005159)

## Full-text entities

- **Genes:** EGFR (epidermal growth factor receptor) [NCBI Gene 1956] {aka ERBB, ERBB1, ERRP, HER1, NISBD2, NNCIS}, VIM (vimentin) [NCBI Gene 7431], BCL2 (BCL2 apoptosis regulator) [NCBI Gene 596] {aka Bcl-2, PPP1R50}, CDH1 (cadherin 1) [NCBI Gene 999] {aka Arc-1, BCDS1, CD324, CDHE, ECAD, LCAM}, CDH2 (cadherin 2) [NCBI Gene 1000] {aka ACOGS, ADHD8, ARVD14, CD325, CDHN, CDw325}, BAX (BCL2 associated X, apoptosis regulator) [NCBI Gene 581] {aka BCL2L4}, MMUT (methylmalonyl-CoA mutase) [NCBI Gene 4594] {aka MCM, MUT}
- **Diseases:** cancers (MESH:D009369), Prostate Cancer (MESH:D011471)
- **Chemicals:** FCM (-)
- **Cell lines:** PC3 — Homo sapiens (Human), Prostate carcinoma, Cancer cell line (CVCL_0035)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC12069013/full.md

## References

40 references — full list in the complete paper: https://tomesphere.com/paper/PMC12069013/full.md

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Source: https://tomesphere.com/paper/PMC12069013