Parthenolide, a Sesquiterpene Lactone, Expresses Multiple Anti-cancer and Anti-inflammatory Activities

Abstract

Parthenolide, a naturally occurring sesquiterpene lactone derived from feverfew (Tanacetum parthenium), exhibits exceptional anti-cancer and anti-inflammatory properties, making it a prominent candidate for further studies and drug development. In this review, we briefly investigate molecular events and cell-specific activities of this chemical in relation to cytochrome c, nuclear factor kappa-light-chain enhancer of activated B cells (NF-κB), signal transduction and activation of transcription (STAT), reactive oxygen species (ROS), TCP, HDACs, microtubules, and inflammasomes. This paper reports that parthenolide shows strong NF-κB- and STAT-inhibition-mediated transcriptional suppression of pro-apoptotic genes. This compound acts both at the transcriptional level and by direct inhibition of associated kinases (IKK-β). Similarly, this review discusses parthenolide-induced ROS-mediated apoptosis of tumor cells via the intrinsic apoptotic signaling pathway. The unique ability of this compound to not harm normal cells but at the same time induce sensitization to extrinsic as well as intrinsic apoptosis signaling in cancer cells provides an important, novel therapeutic strategy for treatment of cancer and inflammation-related disorders.

Rational Design of a Parthenolide-based Drug Regimen That Selectively Eradicates Acute Myelogenous Leukemia Stem Cells

“…As a foundation for rational design of a multidrug regimen, we chose to evaluate parthenolide (PTL), a naturally occurring small molecule with reported anti-tumor properties in nearly all major forms of human cancer (20,21). Of particular interestis the activity of PTL as an agent in AML where it can target bulk tumor cells as well as the relatively rare AML stem cell population (22).…”

Mitigation of monocyte inflammation by inhibition of sodium phosphate co-transporter with phosphonoformic acid and parthenolide in diabetic nephropathy uremia

“…PTN, an inhibitor of NF-κB, could inhibit the systemic inflammation process. Earlier studies have confirmed that PTN could relieve the clinical and pathologic conditions associated with DN in db/db model, as well as decrease the inflammatory factors such as MCP-1 and IL-6 [18,19]. The findings of this study show that the inflammatory factors examined were extremely sensitive to PFA and PTN, as evidenced by the significant reduction of MCP-1 and IL-6 levels in THP-1, as well as the severe intracellular inactivation of p-STAT5 and NF-κB p65 pathways in DNU patients.…”

Targeting Apoptosis Pathways in Cancer and Perspectives with Natural Compounds from Mother Nature

“…All the selected natural compound chemopreventive agents act as potent inhibitors of the NF-kB pathways. Wedelolactone, an inhibitor of IkB kinase, suppressed both TNFa-induced IkB phosphorylation and NF-kB phosphorylation at Ser 536 and Ser 468 (63), parthenolide (64)(65)(66), and honokiol (67,68). Costunolide inhibited the activation of Akt and NF-kB and the expression of antiapoptotic factors B-cell lymphoma-extra large (Bcl-xL) and X-linked inhibitor of apoptosis protein (XIAP) in 11Z cells (69)(70)(71), magnolol inhibits ERK1/2 phosphorylation and NF-kB translocation (72,73), PI3K/Akt/caspase and Fas-L/NF-kB signaling pathways might account for the responses of A375-S2 cell death induced by evodiamine (74,75).…”

“…Some selected agents are part, such as honokiol increases expression and activity of SPH-1 that further deactivates the STAT3 pathway (93), wedelolactone inhibits STAT1 dephosphorylation through specific inhibition of T-cell protein tyrosine phosphatase, which is important tyrosine phosphatase for STAT1 (94). Parthenolide shows strong STAT inhibition-mediated transcriptional suppression of proapoptotic genes (64)(65)(66), and alantolactone inhibits STAT3 activation in HepG2 cells (49). Therefore, these cumulative observations from both in vitro and/or in vivo studies have not only validated STAT as a novel target for cancer chemotherapy, and also hence provided the rationale for developing natural compound STAT inhibitors.…”