**2.1 Cucurbitacin B (1′)**

Cucurbitacin B (CuB) is an oxygenated tetracyclic triterpenoid compound (**1′**). The growth-inhibiting effect of CuB was evaluated on MCF-7 and MDA-MB-231 breast cancer cells and B16F10 melanoma cells by the MTT assay. This compound had antiproliferative effects against breast cancer cells in a dose-dependent manner, and the IC50 values for MCF-7 and MDA-MB-231 were 4.12 and 3.68 μM, respectively [9].

CuB potently suppressed the growth of four types of NSCLC cells (H1299, A549, HCC-827, and H661), inhibiting the proliferation of all the cell lines with IC50 values between 0.05 and 0.130 μM. The mean tumor volume at the end of the study in CuB-treated mice was 200 ± 111 mm3 , compared to 684 ± 321 mm3 in the control group (average reduction of 70% in tumor volume (p < 0.05). No visible sign of toxicity was observed in CuB-treated mice [10]. CuB could suppress human NSCLC cell growth in vitro through its effects on the PI3Kinase and MAPK pathways, which lead to programmed cell death induction, as well as inhibition of cell migration and cell invasion [11]. Additionally, CuB induces cell cycle arrest in A-549 cells and causes DNA double strand breaks. It also produces DNA damage and G2/M phase arrest; this damage could be due to an increase in reactive oxygen species (ROS) formation [12].

 The cytotoxic effect of CuB was tested on HeLa and U2OS cells, and the IC50 values were 12.2 and 17.07 μM, respectively. The inhibition of tubulin polymerization in vitro was observed with an IC50 > 1 mM [13]. CuB from the leaves of Tunisian *E. elaterium* exhibited an anticancer effect and displayed anti-integrin activity in human glioblastoma U87 cells, with no cytotoxicity observed at concentrations up to 500 nM. CuB affected the adhesion and migration of U87 cells to fibronectin with IC50 values of 86.2 and 84.6 nM, respectively. Time-lapse videomicroscopy showed that CuB significantly reduced U87 cell motility and affected directional persistence. CuB also inhibited cell proliferation with an IC50 value of 70.1 nM, as determined using the crystal violet assay. Moreover, CuB inhibited in vitro human microvascular endothelial cell (HMEC) angiogenesis at concentrations up to 10 nM. Interestingly, this work demonstrated for the first time that this effect was specifically mediated by α5β1 integrins. These findings reveal a novel mechanism of action for cucurbitacin B, which displays potential as a specific antiintegrin drug [14].
