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Forskolin, a plant-derived compound, may offer a meaningful improvement in therapies for a highly aggressive leukemia known as KMT2A-rearranged Acute Myeloid Leukemia (KMT2A-r AML). Researchers at the University of Surrey report that this natural molecule could play a valuable role in enhancing patient outcomes.
According to findings published in the British Journal of Pharmacology, forskolin not only slows the growth of leukemia cells but also increases how well chemotherapy drugs work. The Surrey team discovered that forskolin activates Protein Phosphatase 2A (PP2A) and reduces the activity of several cancer-linked genes (MYC, HOXA9 and HOXA10).
Natural Compound Greatly Improves Chemo Sensitivity
The study also identified a notable and unexpected effect. Forskolin made KMT2A-r AML cells far more responsive to daunorubicin, which is a standard chemotherapy option. This improvement did not rely on PP2A activation. Instead, forskolin appeared to interfere with P-glycoprotein 1, a protein that cancer cells use to remove chemotherapy drugs. By limiting the function of P-glycoprotein 1, more daunorubicin remained inside the leukemia cells, increasing the strength of the treatment.
Dr. Maria Teresa Esposito, Senior Lecturer in Biochemistry at the University of Surrey, said:
“Our findings have highlighted an exciting dual mechanism of action for forskolin. Not only does it have direct anti-leukemic effects, but it also acts as a powerful enhancer to conventional chemotherapy. Combining forskolin with daunorubicin could lead to a more effective treatment strategy, potentially allowing for lower doses of chemotherapy and reducing the severe side effects often associated with AML treatments.”
Dr. Simon Ridley, Director of Research and Advocacy at Leukemia UK, says:
“We are committed to funding innovative research and are proud to have supported Dr. Esposito’s work. AML is one of the most aggressive and deadly cancer types, and this study not only deepens our understanding of KMT2A-rearranged AML but also opens the door to kinder, more effective treatments. Work like this is essential if we are to achieve our goal of doubling the five-year survival rate for AML within the next decade.”
Large Research Collaboration Supports Findings
The work was funded by Leukaemia UK and carried out through a broad collaboration involving scientists at the University of Surrey, University of Roehampton, Barts Cancer Institute-Queen Mary University of London, Great Ormond Street Institute of Child Health London- UCL and the Genomic Regulation, CRG Barcelona (Spain).
