Nuclear Factor-kB (NF-kB) Pathway Inhibitor. Parthenolide is a sesquiterpene lactone found in Mexican-Indian medicinal plants such as Tanacetum parthenium. It has been widely used in indigenous medical practices for the treatment of migraine, inflammation and tumors. Parthenolide inhibits? IkB kinase (IKK) and IKKbeta (the upstream activators of the Nuclear Factor-kB (NF-kB) pathway), thus inhibiting Interleukin 1- and tumor necrosis factor a (TNFalpha) without affecting the activation of p38 and c-Jun N-terminal kinase.
In breast adenocarcinoma and pancreatic tumor cell lines which constitutively express active NF-(k)B, parthenolide inhibits NF-(k)B DNA binding and increases sensitivity to chemotherapeutic agents. The sensitivity of these tumor cells to parthenolide is due to the low expression level of the multifunctional detoxification enzyme glutathione S-transferase p caused by inhibition of NF-(k)B activity.