Hyperforin is a prenylated phloroglucinol present in the medicinal plant St John's wort (Hypericum
perforatum). The compound has many biological properties, including antidepressant, anti-inflammatory, antibacterial and
antitumor activities. This review focuses on the in vitro antileukemic effects of purified hyperforin and related
mechanisms in chronic lymphoid leukemia (CLL) and acute myeloid leukemia (AML) – conditions that are known for
their resistance to chemotherapy. Hyperforin induces apoptosis in both CLL and AML cells. In AML cell lines and
primary AML cells, hyperforin directly inhibits the kinase activity of the serine/threonine protein kinase B/AKT1, leading
to activation of the pro-apoptotic Bcl-2 family protein Bad through its non-phosphorylation by AKT1. In primary CLL
cells, hyperforin acts by stimulating the expression of the pro-apoptotic Bcl-2 family member Noxa (possibly through the
inhibition of proteasome activity). Other hyperforin targets include matrix metalloproteinase-2 in AML cells and vascular
endothelial growth factor and matrix metalloproteinase-9 in CLL cells – two mediators of cell migration and angiogenesis.
In summary, hyperforin targets molecules involved in signaling pathways that control leukemic cell proliferation,
survival, apoptosis, migration and angiogenesis. Hyperforin also downregulates the expression of P-glycoprotein, a
protein that is involved in the resistance of leukemia cells to chemotherapeutic agents. Lastly, native hyperforin and its
stable derivatives show interesting in vivo properties in animal models. In view of their low toxicity, hyperforin and its
derivatives are promising antileukemic agents and deserve further investigation in vivo.