Hyperforin, a new lead compound against the progression of cancer and leukemia?

Exploitation of the Bulgarian Flora's Biodiversity as a Source of Immunomodulatory and/or Antineoplastic Agents: Current Challenges and Perspectives

“…Preliminary investigation of the antiangiogenic potential of hyperatomarin revealed that it inhibited the VEGF-induced proliferation of human umbilical vein endothelial cells and induced apoptosis in these cells which fi rmly indicates the need for further examination of the angiostatic effects of this compound. These data well correlate with the recently established potent cytotoxic, pro-apoptotic, antiangiogenic and antimetastatic effects of hyperforin, a structurally related to hyperatomarin acylfl oroglucinol from Hypericum perforatum (6,31).…”

Noxa upregulation is associated with apoptosis of chronic lymphocytic leukemia cells induced by hyperforin but not flavopiridol

“…Expression of Mcl-1 and Bcl-2 was also analyzed, as well as two proteins, which are constitutively overexpressed in CLL cells and downregulated upon flavopiridol and hyperforin-triggered apoptosis: the inducible NO synthase that produces the antiapoptotic NO, and p27kip1 that is cleaved by caspases into a p23 fragment. 4,8 Figure 1 shows that Noxa was expressed at low levels by CLL cells from eight patients (1)(2)(3)(4)(5)(6)(7)(8). In all cases, hyperforin treatment resulted in a strong increase of Noxa expression and this effect was accompanied with stimulation of PARP cleavage (and p27 cleavage in some cases), as compared to untreated controls.…”

“…This member of the Bcl-2 family seems to be crucial in CLL, because its high expression levels are related to apoptosis resistance in vitro and to chemoresistance in vivo. 3 Hyperforin, a natural phloroglucinol, is another inducer of CLL cell apoptosis 4 that exhibits antiangiogenic properties and impairs transporter activities involved in multidrug resistance (see Quiney et al 5 for review). Like flavopiridol, hyperforin acts through the mitochondrial caspase-dependent pathway of apoptosis, but decreases moderately Mcl-1 expression.…”

Hyperforin induces apoptosis of chronic lymphocytic leukemia cells through upregulation of the BH3-only protein Noxa

“…This phloroglucinol purified from Hypericum perforatum (St John's wort) has been characterized as the main active component of this plant used for centuries to treat mild depression. Hyperforin displays antibacterial, antioxidant and immunomodulating activities, inhibits inflammation and allergy mediators, has antitumor, anti-angiogenic and antimigratory effects in vitro and in animal models (20). In CLL cells, hyperforin is capable of inhibiting the production of two mediators of angiogenesis, metalloproteinase-9 and VEGF and the activity of proteins involved in multidrug resistance, as reported by us (21,22).…”