The influence of the secretome from human amniotic mesenchymal stem cells on p53 and MDM2 expression in MDA-MB-231 breast cancer cell line

Breast cancer ranks as the foremost cause of death among women worldwide. Despite the availability of various treatment options such as chemotherapy, radiotherapy, and hormone therapy, these current strategies are often ineffective and thereby, there is a constant necessity to explore new therapeutic avenues with minimal side effects and enhanced efficacy. The application of cell-based therapy and the use of stem cells or their derivatives in treating diseases, including cancer, have become well established. Herein, we aimed to investigate the impact of the secretome of human amniotic mesenchymal stem cells (hAMSCs) on MDA-MB-231 cancer cells (with a mutant p53 R280K background) focusing on the p53/MDM2/p21/ATM/ATR/PUMA/Bax/Caspase3 signaling pathways.

To achieve this, we developed a co-culture system utilizing 6 well plates transwell. After 72 h, cell death and cell cycle arrest in hAMSCs-treated MDA-MB-231 cells were assessed by analyzing the aforementioned signaling pathways using Western blot and flow cytometry. The exposure time for MTT assay was 48 h, and for DAPI staining, it was 24 h.

Our results revealed an increase in the expression levels of ATM, ATR, CHK2, p53, p-p53, PUMA, Bax, cleaved caspase 3, p21, RB, and p-RB, alongside a reduction in MDM2 expression.

These findings suggest that hAMSCs secretome promotes cell death and induces S phase cell cycle arrest in MDA-MB-231 cells, suggesting its potential as a novel approach in cancer therapy.