Doxorubicin-Induced Cytotoxicity in Adipose-Derived Stem Cells Is Associated With Altered SAPK/JNK Signaling

Adipose-derived stem cells (ADSCs) are widely used in regenerative medicine, but their functionality declines under chemotherapeutic stress. Doxorubicin (Dox) is an effective anticancer agent known to induce long-term toxicity in healthy tissues. Increasing evidence suggests that Dox promotes cellular dysfunction, including apoptosis, promotion of oxidative stress, and premature senescence. The SAPK/JNK signaling pathway is implicated in stress responses and may contribute to Dox-induced aging in stem cells. However, its role in ADSC senescence and functional decline remains unclear. This study evaluated the effects of Dox on ADSC viability and aging-associated processes, with a focus on SAPK/JNK signaling. ADSCs exposed to 0.1-100 μM Dox for 24 h showed reduced mitochondrial activity and ATP levels at clinically relevant doses (5 μM), along with disrupted cell cycle progression and cytoskeletal alterations. Dox induced both apoptosis and premature senescence and increased oxidative stress. These effects were accompanied by alterations in SAPK/JNK pathway expression. Overall, Dox promoted ADSC dysfunction, highlighting potential limitations in the therapeutic use of ADSCs during chemotherapy and emphasizing the need for protective strategies. Alterations in the SAPK/JNK signaling pathway were observed in response to Dox-induced stress, suggesting that this pathway may contribute to the cellular stress response. These findings suggest that the development of approaches to preserve ADSC function and mitigate Dox toxicity is critical for improving the safety and efficacy of regenerative medicine applications.