Cucurbitacin D, a triterpenoid isolated from Ecballium elaterium (L.), exhibits anticancer and antitumor activity, inhibits glucose uptake and lactate production in metastatic PrC, and induces inflammasome activation independent of ERK1/2 activation. Cucurbitacin D, a novel inflammasome activator in macrophages, inhibits HepG2 cell proliferation and induces apoptosis by modulating the JAK/STAT3, PI3K/Akt/mTOR and MAPK signaling pathways, and can be used in the study of cervical cancer, leukemia, and prostate cancer.

Immunomodulating activities of Cucurbitacin D were investigated in macrophages. Cucurbitacin D could increase LPS-induced interleukin (IL)-1β production in culture supernatant of THP-1 cells, peritoneal exudate cells (PECs), bone marrow derived macrophages (BMDMs), and RAW264 cells. At the transcriptional level, Cucurbitacin D enhanced LPS-induced IL-1β mRNA expression through activation of ERK1/2 mitogen-activated protein kinases (MAPKs). At the posttranscriptional level, the activation of caspase-1 induced by Cucurbitacin D has also been demonstrated following treatment with a caspase-1 inhibitor and siRNA. Importantly, Cucurbitacin D has further been shown to induce inflammasome activation independent of ERK1/2 activation. Western blotting showed interaction of NOD-like receptor family, pyrin domain containing 3 (NALP3) and apoptosis-associated speck-like protein containing a caspase-activating and recruitment domain (ASC), suggesting activation of the inflammasome and a possible reason for activation of caspase-1[1]