Molecular mechanisms of parthenolide’s action: Old drug with a new face.
Parthenolide, a sesquiterpene lactone derived from the Tanacetum parthenium (feverfew) shows anticancer activities in a variety of cell lines. It interacts with nucleophilic sites of biologically important molecules.
In addition, inhibition of STAT and MAP kinase activities and the induction of sustained JNK activity as well as p53 activity via influencing MDM2 and HDAC1 levels lead to an increased susceptibility of cancer cells to chemo- and radiotherapy.
At the epigenetic level, parthenolide reduces HDAC1 level and, by inhibiting DNMT2 activity, induces global hypomethylation of DNA, which can restore the expressions of some suppressor genes. A unique property of Parthenolide is its ability to induce cell death mainly in cancer cells, while sparing healthy ones and it also protects normal cells from UVB and oxidative stress. More remarkably, it seems to have the potential to target some cancer stem cells.
Koprowska K, Czyż M. Molecular mechanisms of parthenolide’s action: Old drug with a new face. 2010. Postepy Hig Med Dosw, Vol 64. pp.100-114
The natural products parthenolide and andrographolide exhibit anti-cancer stem cell activity in multiple myeloma.
Multiple myeloma (MM) is an incurable plasma cell malignancy where nearly all patients succumb to a relapse. The current preclinical models of MM target the plasma cells, constituting the bulk of the tumor, leaving the cancer stem cells to trigger a relapse. Utilizing a three-dimensional tissue culture system where cells were grown in extracellular matrix designed to reconstruct human bone marrow, we tested the anti-multiple myeloma cancer stem cell (MM-CSC) potential of two natural product inhibitors of nuclear factor κB (NFκB). Here we show that parthenolide and andrographolide are potent anti-MM-CSC agents. Both natural products demonstrated preferential toxicity toward MM-CSCs over non-tumorigenic MM cells. Addition of the bone marrow stromal compartment abrogated andrographolide activity while having no effect on parthenolide cytoxicity. This is the first report of a natural product with anti-CSC activity in myeloma, suggesting that it has the potential to improve the survival of patients with MM by eliminating the relapse-causing MM-CSCs.
Gunn EJ, Williams JT, Huynh DT et al. Leuk Lymphoma. 2011 Jun;52(6):1085-97. Epub 2011 Mar 21.