Vitamin C: Friend or Foe? “Unveiling Interaction with Parthenolide, Vincristine, miR-17-5p, miR-125b-5p, miR-181b-5p Expression, and Apoptosis in NALM6 Cell Line

Background: B-acute lymphoblastic leukemia (B-ALL) presents significant global public health challenges. Objectives: This study aimed to evaluate the effect of vitamin C alone and in combination with vincristine or parthenolide, focusing on changes in miR-17-5p, miR-125b-5p, and miR-181b-5p in a B-ALL cell model (NALM6 cell line). Methods: In this experimental study, cell viability was determined through the MTT assay and propidium iodide (PI) staining. Flow cytometry was applied to evaluate apoptosis. The expression of miRNAs was assessed using real-time polymerase chain reaction (RT-PCR). Molecular docking was utilized to validate that miR-17-5p, miR-181b-5p, and miR-125b-5p were modulated by vitamin C, parthenolide, and vincristine treatment. Results: Propidium iodide staining revealed that vitamin C (0.5 mM) reduced cell viability by nearly 50%. Flow cytometry analysis further demonstrated that combining vitamin C (0.5 mM) with either vincristine (0.8 nM) or parthenolide (1.925 µM) increased apoptosis compared to untreated controls. The combination treatments induced apoptosis in 79.22% of cells treated with vitamin C and vincristine, and 82.52% of cells treated with vitamin C and parthenolide, respectively. Real-time PCR analysis showed a decrease in the expression of all three miRNAs. Notably, the combination therapies further decreased their expression, suggesting potential involvement in the observed enhanced apoptosis. Further, molecular docking validated the modulation of these microRNAs (miRNAs) by vitamin C and its combinatory conditions. Conclusions: These findings suggest that vitamin C may improve the effectiveness of vincristine or parthenolide in inducing apoptosis in NALM6 leukemia cells. The modulation of miR-17-5p, miR-125b-5p, and miR-181b-5p expression likely plays a role in the synergistic effect. Overall, this evidence supports the potential application of vitamin C as an adjunct therapy for B-ALL.