Gallic acid enhances the efficacy of BCR::ABL1 tyrosine kinase inhibitors in chronic myeloid leukemia.
Gallic Acid Enhances the Efficacy of BCR::ABL1 Tyrosine Kinase Inhibitors in Chronic Myeloid Leukemia through Inhibition of Mitochondrial Respiration and Modulation of Oncogenic Signaling Pathways.
AI Summary
Key Findings
Abstract
While BCR::ABL1 tyrosine kinase inhibitors have transformed the treatment paradigm for chronic myeloid leukemia (CML), disease progression and treatment resistance due to BCR::ABL1-dependent and BCR::ABL1-independent mechanisms remain a therapeutic challenge. Natural compounds derived from plants have significantly contributed to cancer pharmacotherapy. This study investigated the efficacy of an active component of, a local medicinal plant, in CML. Using high-performance liquid chromatography-electrospray ionization-mass spectrometry, a chemical constituent fromextract was isolated and identified as gallic acid. Commercially obtained gallic acid was used as a chemical standard. Gallic acid frominhibited proliferation and induced apoptosis in CML cell lines, as did the chemical standard. Furthermore, gallic acid induced apoptosis and decreased the colony formation of primary CML CD34cells. The combination of isolated gallic acid or its chemical standard with BCR::ABL1 tyrosine kinase inhibitors resulted in a significantly greater inhibition of colony formation and cell growth compared to a single drug alone. Mechanistically, CML cells treated with gallic acid exhibited the disruption of multiple oncogenic pathways including ERK/MAPK, FLT3 and JAK/STAT, as well as impaired mitochondrial respiration. Rescue studies showed that gallic acid is significantly less effective in inducing apoptosis in mitochondrial respiration-deficientρcells compared to wildtype cells, suggesting that the action of gallic acid is largely through the inhibition of mitochondrial respiration. Our findings highlight the therapeutic potential ofin CML and suggest that gallic acid may be a promising lead chemical constituent for further development for CML treatment.
Affiliation
Wei Xiang
External References
- PubMed ID:
- 39063200
Comments
Sign in or create a free account to join the conversation.
Sign in to commentBe the first to comment.