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  • Synergistic Interaction of Resveratrol and Sorafenib in NALM-6 B-Cell Precursor Acute Lymphoblastic Leukemia Cells

  • Mobina Nakhaei Shamahmood,1 Fatemeh Mezginejad,2,* Zahra Salehi,3
    1. Department of Hematology, Faculty of Medical Science, Tarbiat Modares University, Tehran, Iran.
    2. Department of Hematology, School of Allied Medicine, Cardiovascular Diseases Research Center, Birjand University of Medical Sciences, Birjand, Iran.
    3. Cell Therapy and Hematopoietic Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran.


  • Introduction: Acute lymphoblastic leukemia (ALL) is a biologically heterogeneous malignancy characterized by diverse molecular alterations and variable treatment responses. Identifying effective drug combinations that target complementary cellular pathways may help address therapeutic resistance. Resveratrol and sorafenib have demonstrated antileukemic activity through distinct mechanisms; however, their combined effects in B-cell precursor ALL remain poorly characterized. This study evaluated the cytotoxic interaction of resveratrol and sorafenib in NALM-6 cells.
  • Methods: NALM-6 B-cell precursor ALL cells were treated with increasing concentrations of resveratrol (25–200 µM) and sorafenib (5–30 µM), alone or in combination, for 24, 48, and 72 hours. Cell viability was assessed using the MTT assay, and IC₅₀ values were determined. Drug interactions were evaluated using the Chou–Talalay combination index (CI) method, with CI <1 indicating synergism, CI =1 an additive effect, and CI >1 antagonism.
  • Results: Resveratrol and sorafenib independently reduced NALM-6 cell viability in a concentration- and time-dependent manner. At 48 hours, the IC₅₀ values were approximately 100 µM for resveratrol and 15 µM for sorafenib. Combined treatment produced a greater reduction in cell viability than either agent alone. Importantly, the drug interaction shifted from an approximately additive effect at 24 hours (CI = 0.98 ± 0.03) to synergism at 48 hours (CI = 0.50 ± 0.02) and 72 hours (CI = 0.48 ± 0.01), demonstrating a time-dependent enhancement of the antileukemic effect.
  • Conclusion: Resveratrol enhanced the antileukemic activity of sorafenib in NALM-6 B-cell precursor ALL cells, with the interaction progressing from an approximately additive effect to clear synergism over time. These findings support further investigation of this combination in genetically diverse ALL models. Molecular and genomic studies are warranted to clarify the mechanisms underlying this synergistic interaction and identify potential biomarkers of treatment response.
  • Keywords: Acute lymphoblastic leukemia; NALM-6; Resveratrol; Sorafenib; Drug synergy

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