Cucurbitacin I is triterpenoid compound that acts as a potent inhibitor of the STAT3/JAK signaling pathway. It specifically suppresses levels of tyrosine phosphorylated STAT3 in v-Src-transformed NIH 3T3 cells and in A549 cells (IC50 = 500 nM) resulting in inhibition of STAT3 DNA binding and reduced STAT3-mediated gene transcription. It also suppresses JAK2 phosphorylation but does not affect Src, ERK, JNK or Akt. In nude mice, cucurbitacin I
(1 mg/kg/day) suppressed growth of various tumors expressing constitutively active STAT3. It promotes the differentiation of dendritic cells and macrophages and enhances the effect of cancer immunotherapy. Cucubitacin I (1 μM for 2 hours) reduced clonogenicity of nasopharyngeal carcinoma cells in vitro and suppresses tumor growth in mice (1.3 mg/kg).
