# Concentrated Growth Factor Induces ER Stress and Apoptosis by Increasing Ceramide Generation in Selected Tumour Cell Lines

## TL;DR

This study shows that concentrated growth factor can selectively kill certain cancer cells by causing stress and cell death through specific biological pathways.

## Contribution

The paper reveals a novel mechanism by which CGF induces cancer cell death via ER stress, mitochondrial dysfunction, and lipid metabolism changes.

## Key findings

- CGF-CM selectively induces cytotoxic effects in MCF7 and SaOS-2 cells.
- CGF-CM increases ceramide and triglyceride levels, linking lipid metabolism to cancer cell death.
- ER stress markers and mitochondrial dysfunction are key in CGF-CM-induced apoptosis.

## Abstract

Concentrated growth factor (CGF), a blood‐derived autologous biomaterial, is increasingly utilised in regenerative medicine and, recently, in cancer‐related surgeries. Rich in cytokines, platelets, nucleated cells and fibrin scaffolds, CGF offers therapeutic promise but requires rigorous safety evaluation in oncology. This study explores the effects of CGF‐conditioned medium (CGF‐CM) on breast cancer (MCF7, MDA‐231) and osteosarcoma (SaOS‐2, MG‐63) cell lines. Our findings reveal that CGF‐CM selectively induces cytotoxic effects in MCF7 and SaOS‐2 cells, while no cytotoxicity was observed in MDA‐231 and MG‐63 cells. Early apoptosis in MCF7 and SaOS‐2 cells was accompanied by mitochondrial dysfunction, evidenced by an increased BAX/BCL‐2 ratio and cytochrome c release. CGF‐CM treatment also elevated ceramide and triglyceride levels, linking lipid metabolic changes to cancer cell death. Endoplasmic reticulum (ER) stress markers, ATF6 and XBP1, were significantly upregulated in MCF7 and SaOS‐2 cells, highlighting the role of ER stress in CGF‐CM‐induced cytotoxicity. Furthermore, CGF‐CM inhibited autophagic flux, as demonstrated by altered LC3 and p62 protein levels, disrupting cellular homeostasis and contributing to apoptosis. These findings highlight the selective cytotoxic effects of CGF‐CM on specific cancer cell lines. The intricate interplay between mitochondrial dysfunction, ER stress, autophagy inhibition and lipid metabolism highlights its complex mechanisms of action.