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Cucurbitacin I is a selective inhibitor of JAK2/STAT3 signaling pathway with an IC50 value of 500 nM in A549 (a human lung adenocarcinoma cell line). It suppressed phosphotyrosine levels of STAT3, restrained STAT3 DNA binding and STAT3-mediated gene expression but had no effects on the activation of Src, Akt, ERK and JNK [1].
JAK/STAT3 signaling is well known for its vital role in the regulation of tumor cell proliferation, survival, invasion and immunosuppression. It promotes the development of various types of cancer in different manners [2].
Cucurbitacin I is often used to investigate the role of STAT3 in tumor development. It can induce apoptosis and block cell cycle progression of various cancer cells. In addition, Cucurbitacin I can decrease cell viability through inhibiting cell migration and invasion and enhancing chemosensitivity in the colon cancer cell line COLO205 [3].
Recent research has showed that it also has anti-angiogenic effects in human breast cancer cells [4]. In vivo, matrigel plug assay showed dramatic decrease in vascularization and hemoglobin content in the plugs from Cucurbitacin-I-treated mice, compared with control mice [5]. Therefore, Cucurbitacin I has potent anticancer effect on a variety of cancer cell types.
However, exposing glioblastoma multiforme cells to Cucurbitacin I could up-regulate beclin1 and trigger a protective autophagy against the apoptosis. Deletion of beclin 1 or treatment with the autophagy inhibitor sensitized cancer cells to Cucurbitacin I-induced apoptosis [6]. Thus the role of Cucurbitacin I in the regulation of autophagy requires for further research.
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