Testosterone Propionate: Dual Impact on Bone Marrow Mesenchymal Stem Cells and Anti-Cancer Potential

General Description

Testosterone propionate has proven to be a potent promoter of bone marrow mesenchymal stem cells (BM MSCs) division, with a concentration of 10-8 M showing the highest proliferation rate and enhanced viability. Additionally, Testosterone propionate exhibits anti-cancer potential by reducing viability of leukemia cells in co-culture with BM-MSCs. The hormone induces changes in BM-MSC phenotype and morphology, suggesting modulation of inflammatory signaling pathways. These findings highlight Testosterone propionate's dual impact in boosting BM MSCs' functions and exerting direct cytotoxic effects on cancer cells, offering promising avenues for therapeutic exploration in cancer treatment.

Figure 1. Testosterone propionate

Promotion of Bone Marrow Mesenchymal Stem Cells

Enhanced Division of Bone Marrow Mesenchymal Stem Cells

Testosterone propionate has been shown to significantly promote the division of bone marrow mesenchymal stem cells at all concentrations tested. This proliferative effect was particularly pronounced at a concentration of 10-8 M, where the highest division rate was observed compared to other TP concentrations. Interestingly, even the vehicle group demonstrated increased cell division compared to the control group, indicating the potential stimulatory impact of the solvent alone on BM MSCs.

Viability and Apoptosis Modulation

Furthermore, Testosterone propionate treatment did not influence early apoptosis or necrosis levels in BM MSCs. However, viability rates were significantly higher in TP-treated groups, except for the 10-6 M concentration, which exhibited decreased viability and higher late apoptosis rates compared to the vehicle and control groups. This suggests that high doses of TP may have a cytotoxic effect on BM MSCs. Notably, Testosterone propionate was found to mitigate the cytotoxic impact of the solvent, as indicated by higher viability rates in TP-treated groups compared to the vehicle group. Additionally, late apoptosis rates were lower in the 10-7 and 10-8 M TP groups compared to the vehicle, further supporting the potential protective role of TP against solvent-induced toxicity. 

Based on these findings, further studies were focused on the 10-8 M concentration of Testosterone propionate due to its pronounced proliferative effects and relatively lower cytotoxicity compared to higher concentrations. The results suggest that Testosterone propionate has the potential to enhance cell division and viability of BM MSCs, making it a promising candidate for further investigation in the context of promoting tissue regeneration and repair. ¹

Anti-cancer Potential

Influence on Bone Marrow-Derived Mesenchymal Stem Cells

Testosterone propionate has shown promising potential as an agent with anti-cancer properties, particularly in the context of influencing the behavior of bone marrow-derived mesenchymal stem cells and their interaction with cancer cells. In a recent study, the presence of Testosterone propionate at a concentration of 10-8 M significantly reduced the viability of K562 cells, a chronic myelogenous leukemia cell line, when co-cultured with BM-MSCs compared to control conditions (p < 0.01). Notably, pre-treatment of BM-MSCs with TP prior to co-culture also demonstrated a notable decrease in K562 cell viability, albeit to a lesser extent (p < 0.05). 

Direct Cytotoxic Effects on Cancer Cells

Interestingly, Testosterone propionate alone exhibited cytotoxic effects on K562 cells, although this effect did not reach statistical significance (p > 0.05). This suggests that TP may directly impact cancer cell viability independent of BM-MSCs. Additionally, Testosterone propionate treatment induced distinct changes in BM-MSCs, as observed through confocal microscopy, indicating a shift towards an inflammatory phenotype characterized by increased CXCL9 staining and decreased CXCL5 expression compared to control conditions. Furthermore, TP altered the cellular morphology of BM-MSCs, leading to broader cell bodies in the treated group, contrasting with the spindle-shaped morphology of cells in the control group. 

These findings underscore Testosterone propionate's dual impact: it not only enhances the cytotoxicity of BM-MSCs against K562 cells but also exerts direct cytotoxic effects on the cancer cells themselves. The observed changes in BM-MSC phenotype and morphology suggest a potential mechanism involving inflammatory signaling modulation, which could contribute to its anti-cancer properties. Further elucidation of these mechanisms could lead to novel therapeutic strategies harnessing Testosterone propionate's potential in cancer treatment, particularly in leukemia and potentially other malignancies where BM-MSCs play a significant role in the tumor microenvironment. ¹

Reference

1. Aru B, Akdeniz T, Da?deviren H, Gürel G, Yan?kkaya Demirel G. Testosterone Propionate Promotes Proliferation and Viability of Bone Marrow Mesenchymal Stem Cells while Preserving Their Characteristics and Inducing Their Anti-Cancer Efficacy. Balkan Med J. 2023; 40(2): 117-123.

You may like