Assessing the Protective Role of Wharton's Jelly-Derived Mesenchymal Stem Cell Secretomes in Inducing Apoptosis in SKBR3 Breast Carcinoma Cells

Background: Breast carcinoma (BC) is the most prevalent form of cancer in women and is classified into various subtypes based on the expression of ER, PR, and human epidermal growth factor 2 (HER2) receptors. Human epidermal growth factor 2-positive BC, in particular, presents significant challenges due to its aggressiveness and limited treatment options. Modulating apoptotic pathways is crucial for reducing tumor burden and enhancing treatment efficacy. Objectives: This study aimed to evaluate the inhibitory effects of secretomes derived from Wharton's jelly mesenchymal stem cells (WJ-MSC secretomes) on the proliferation of the SKBR3 cell line, as well as the subsequent changes in apoptosis-related gene expression after treatment. The research provides new insights into the therapeutic potential of WJ-MSC secretomes for HER2-positive BC. Methods: SKBR3 cells were exposed to WJ-MSC secretomes at doses of 10, 25, and 50 μg/mL for 24 and 48 hours. MTT assays and colony formation assays were used to evaluate cell viability, while annexin V/PI staining and mRNA expression analyses were conducted to assess apoptosis. Results: Treatment with WJ-MSC secretomes led to a significant, concentration- and time-dependent reduction in colony numbers and cell viability in the 25 and 50 μg/mL groups. Early and late apoptotic indices increased significantly in the 25 μg/mL group, with P-values of < 0.01 and < 0.05, respectively. The mRNA expression levels of Caspase-9 (P < 0.001), Caspase-3 (P < 0.05), and the Bax/Bcl-2 ratio (P < 0.01) significantly increased in the 25 μg/mL treatment group. Caspase-8 activity was unaffected by WJ-MSC secretomes. Conclusions: Wharton's jelly mesenchymal stem cells secretomes demonstrate potential as an anticancer agent for HER2-positive BC, acting through the intrinsic apoptotic pathway in a concentration- and time-dependent manner. This study is the first to detail the specific effects of WJ-MSC secretomes on HER2-positive SKBR3 cells, suggesting their novel application in targeted breast cancer therapy.