**2.7. MSCs can induce apoptosis of cancer cells and endothelial cells**

Depending on the microenvironment, MSCs can exert an antiproliferative effect. Lu et al. demonstrated that MSCs had an inhibitory effect on mouse tumor hepatoma cells in a cell-dependent manner through the activation of intrinsic caspase 3 pathway [107]. Lu et al. reported that MSCs increased p21 gene expression, involved in the arrest of the cell cycle. These data demonstrate that MSCs exerted tumor inhibitory effects in the absence of host immunosuppression, inducing arrest of the G0/G1 phase and apoptosis of cancer cells [107]. The same tumor suppressor activity by MSCs was observed in xenografted SCID mice with disseminated non-Hodgkin lymphoma [108]. A single injection of MSCs which increased the survival of the animals included those who presented more aggressive lymphomas. In turn, significant induction of endothelial cell apoptosis was observed when co-cultured with MSCs, suggesting that MSCs exert anti-angiogenic activity through endothelial cell apoptosis [108]. These findings were consistent with the results reported by Karnoub et al. where they demonstrated that MSCs exhibited potent anti-angiogenic activity in Kaposi's sarcomas with high vascularity and endothelial cell cultures in vitro by inducing apoptosis of tumor epithelial and endothelial cells through the Dkk-1 protein [32, 34]. Additionally, Dasari et al. reported that downregulation of the antiapoptotic inhibitor, inhibitor of the apoptosis protein linked to X (XIAP), in the presence of human umbilical cord bloodderived mesenchymal stem cell (hUCBSC) induced apoptosis of glioma cells and xenograft by the activation of caspase-3 and caspase-9 [109]. Recently, MSCs cultured at high density express IFN type I, which leads to cell death of breast cancer cells, MCF-7 and MDR-MB-231 cells [98]. In addition, MSCs prepared with IFN-gamma or cultured with three-dimensional systems can express TRAIL, which induces specific apoptosis of tumor cells. [97, 98].
