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Study Finds Novel Compound Reduces Survival of Imatinib-Resistant CML Cells

By: Sarah Campen, PharmD
Posted: Tuesday, March 12, 2019

A novel hybrid compound, NPQ-C6, appears to reduce the survival of chronic myeloid leukemia (CML) cells, even those resistant to imatinib. By inhibiting the STAT5 pathway, the naphthoquinone-coumarin conjugate blocks the expression of genes that facilitate cell-cycle progression, survival of CML cells, and oncogenesis. A study highlighting the compound as a “promising scaffold” for drug design was published in Frontiers in Pharmacology.

“These findings provide new insights into [the] molecular mechanism of naphthoquinone-coumarin conjugates in cancer,” stated Leandro Fernández-Pérez, MD, PhD, of the Universidad de Las Palmas de Gran Canaria, Las Palmas, Spain, and colleagues. “[They] support its potential therapeutic application in BCR-ABL– and STAT5-related malignancies.”

The effects of NPQ-C6 were evaluated on human CML-derived K562 cells. The researchers found that NPQ-C6 triggered cell-cycle arrest by changing expression levels and/or phosphorylation of many proteins involved in cell-cycle progression. The compound also induced apoptosis in K562 cells, possibly by initiating the mitochondrial apoptotic pathway.

NPQ-C6 decreased levels of PIM-1, a protein that promotes cell cycling, proliferation, and cell survival in hematologic malignancies. Dr. Fernández-Pérez and colleagues noted that targeting PIM kinases “may provide a unique therapeutic approach for the treatment of BCR-ABL1–positive leukemia.” Finally, NPQ-C6 was able to maintain its activity on the BCR-ABL1/STAT5/c-MYC/PIM-1 oncogenic pathway in imatinib-resistant cells, suggesting that naphthoquinone-coumarin conjugates could circumvent resistance to tyrosine kinase inhibitors in BCR-ABL1–positive leukemia.

Disclosure: The study authors reported no conflicts of interest.



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