Evaluation of the effects of silver nanoparticles and ciprofloxacin on apoptotic gene expression (BAX, Bcl-2, and caspase-3) in NALM-6 acute lymphoblastic leukemia progenitor B cells.

Acute lymphoblastic leukemia (ALL), classified as a lymphoid neoplasm under the WHO 5th Edition Haematolymphoid Tumours system, is characterized by uncontrolled proliferation of immature B-cell precursors. Nanotechnology-based therapies are promising for hematologic malignancies because they modulate cellular pathways and improve drug delivery without directly targeting apoptotic proteins. This study investigates the effects of silver nanoparticles (Ag-NPs), known for their anti-cancer and oxidative stress-mediated cytotoxic properties, and ciprofloxacin, a fluoroquinolone with reported anti-leukemic activity, on apoptosis-related gene expression in NALM-6 B-cell progenitor ALL cells. Cells were treated with ciprofloxacin (25 µg/mL) or Ag-NPs (4 µg/mL), alone or combined, for 48 h, followed by MTT assay for viability, Annexin V-FITC/PI flow cytometry for apoptosis, and real-time PCR analysis of BAX, B-cell lymphoma 2 (Bcl-2), and Caspase-3 expression (normalized to glyceraldehyde-3-phosphate dehydrogenase [GAPDH]). Ciprofloxacin significantly increased pro-apoptotic BAX and Caspase-3 expression (p = 0.0001, p = 0.0113) while reducing anti-apoptotic Bcl-2 (p = 0.0013); Ag-NPs produced moderate apoptotic effects, whereas combination treatment enhanced apoptosis (31.0%, p = 0.0092) and further amplified gene modulation (e.g., BAX log2FC = 4.4531, p = 0.0036). These findings suggest that Ag-NPs may enhance upstream signaling and drug response rather than directly acting on apoptotic proteins, supporting their potential as nanotechnological co-therapeutics in B-cell ALL. Further mechanistic and in vivo studies are warranted.