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Background/aim <p>Conditioned media derived from Mesenchymal stem cells (MSC-CM) was suggested as a promising alternative cell-free regenerative therapy. It is hypothesized that the synergistic effect of MSC-CM with anticancer drugs may improve their antiproliferative and antimetastatic effects against cancer cells. Herein, the MSC-CM was impregnated with Wortmannin, a pan-PI3K/Akt/mTOR inhibitor, and their combined effect was investigated against breast cancer cells.</p> Materials and methods <p>To explore this, the cytotoxic, apoptotic, and autophagic potentials were assessed in luminal-A breast cancer cells (MCF-7).</p> Results <p>We found that incubation of MCF-7 to Wort-containing-CM induced apoptosis- and autophagy-mediated cell death, meanwhile prolonged exposure caused massive necrotic cell death. The involvement of MSC-CM effectively reduced Wortmannin IC50 observed in Wort-treated cells. Also, Wort-loaded-CM induced nuclear DNA fragmentation and reduced in vitro cell migration. These findings were associated with a Wort-dependent reduction in cell viability, the formation of the phosphorylated Akt and mTOR proteins, reduced the expression of mRNA, and downregulated the expression of the catalytic domain of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K-Ca).</p> Conclusion <p>These findings revealed the promising antiproliferative and antimetastasis effects of combining pan-PI3K/Akt/mTOR inhibitors with MSC-derived-CM in breast cancer via the downregulation of PI3K/AKT/mTOR signaling pathways. Further studies are required to validate this chem-regenerative strategy in cancer treatment.</p>

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Impregnation of mesenchymal stem cell conditioned media with wortmannin enhanced its antiproliferative effect in breast cancer cells via PI3K/Akt/mTOR pathway

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年3月4日

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  • Doha F. Ismail,
  • Mai M. El-Keey,
  • Saad M. Elgendy,
  • Mohamed Hessien

摘要

Background/aim

Conditioned media derived from Mesenchymal stem cells (MSC-CM) was suggested as a promising alternative cell-free regenerative therapy. It is hypothesized that the synergistic effect of MSC-CM with anticancer drugs may improve their antiproliferative and antimetastatic effects against cancer cells. Herein, the MSC-CM was impregnated with Wortmannin, a pan-PI3K/Akt/mTOR inhibitor, and their combined effect was investigated against breast cancer cells.

Materials and methods

To explore this, the cytotoxic, apoptotic, and autophagic potentials were assessed in luminal-A breast cancer cells (MCF-7).

Results

We found that incubation of MCF-7 to Wort-containing-CM induced apoptosis- and autophagy-mediated cell death, meanwhile prolonged exposure caused massive necrotic cell death. The involvement of MSC-CM effectively reduced Wortmannin IC50 observed in Wort-treated cells. Also, Wort-loaded-CM induced nuclear DNA fragmentation and reduced in vitro cell migration. These findings were associated with a Wort-dependent reduction in cell viability, the formation of the phosphorylated Akt and mTOR proteins, reduced the expression of mRNA, and downregulated the expression of the catalytic domain of phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K-Ca).

Conclusion

These findings revealed the promising antiproliferative and antimetastasis effects of combining pan-PI3K/Akt/mTOR inhibitors with MSC-derived-CM in breast cancer via the downregulation of PI3K/AKT/mTOR signaling pathways. Further studies are required to validate this chem-regenerative strategy in cancer treatment.