Abstract 4197: Synergic antioxidant effect of cord blood stem cells derived exosomes and sulforaphane on CML

Abstract Despite the promising advances in the diagnostics and therapeutics of Chronic Myeloid Leukaemia in recent years, they are still the disease of the era. Conventional treatments cause severe side effects, including death. Investigating novel drugs and combination therapies is essential for improving and advancing leukaemia and treatment. In the context of haematological cancers, elevated levels of reactive oxygen species (ROS) can induce oxidative stress. This oxidative stress may be mitigated by the administration of increased antioxidant levels. sulforaphane (SFN) is an antioxidant compound found mainly in cruciferous vegetables. Many studies demonstrated that the biological properties of SFN make it a suitable candidate for blood cancer treatment, including the activation of several metabolic processes and induction of apoptosis in cancer cells. Also, In the last few years, the ability of human cord blood stem cells (CBSC)-derived exosomes to mediate cellular communication has been extensively investigated. CBSC exosomes have proved beneficial in treating various diseases. This study aimed to investigate the impact of CBSC exosomes and SFN in vitro on haematological disease in general and CML in particular, compared to healthy controls. The Comet assay was used to assess the impact of SFN and CBSC exosomes on DNA damage, as well as to evaluate the potential genoprotective effects of these treatments at the presence of H2O2 exposure. A high level of DNA damage was observed in blood cancer (such as lymphoma and multiple myeloma) PMBCs compared to healthy controls. In this study involving PMBCs from cancer patients (N=20) and healthy controls (N=20), treatment with two concentrations of sulforaphane (SFN) (10 and 15µM), along with the application of 12% v/v CBSC exosomes, demonstrated a significant reduction in DNA damage induced by hydrogen peroxide (H2O2), with a p-value(p<0.001). The doses employed in this study had a minimal impact on the viability of healthy cells while demonstrating a noticeable reduction in cell viability among CML cells, as assessed by the CCK-8 assay. In this research we utilised qPCR and Western Blotting techniques to investigate the influence of SFN and hCBSC-derived exosomes, as well as SFN-CBSC exosomes, on the gene and protein expression related to the apoptosis pathway in CML cells. This study focused on key markers such as p53, p21, Bcl-2 genes and proteins, and Caspase-3, in addition to examining the BCR-ABL gene associated with tumorigenicity. We found that all previous treatments were able to induce apoptosis and reduce the oncogenicity of CML compared to negative control. Citation Format: Banan Majid Alkhatabeh, Shohreh Jafarinejad, Mohammad Isreb, Farshid Sefat, Saeed Heidari, Adi Baumgartner, Mojgan Najafzadeh. Synergic antioxidant effect of cord blood stem cells derived exosomes and sulforaphane on CML [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2025; Part 1 (Regular Abstracts); 2025 Apr 25-30; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2025;85(8_Suppl_1):Abstract nr 4197.