Differentiation of SWO-38 glioma cells induced by CDA-2 is mediated by peroxisome proliferator-activated receptor gamma.

Glioma remains one of the most lethal human tumors in spite of the progress in radiotherapy, chemotherapy, and surgical techniques. Cell differentiation agent-2 (CDA-2) is an extraction from healthy human urine consisting of primary organic acids and peptides, and it has been demonstrated to inhibit growth and induce differentiation in glioma and other cell lines. However, the mechanism remains unclear. Peroxisome proliferator-activated receptors (PPARs) are members of the nuclear hormone receptors (NHRs) which are involved in cellular differentiation and proliferation. In this study, we investigated if CDA-2 induced differentiation of SWO-38 glioma cells is mediated by PPARgamma. CDA-2 induced differentiation of SWO-38 cells was characterized by typical morphological changes, increased expression of GFAP, inhibition of proliferation and G(0)/G(1) cell cycle arrest. CDA-2 also triggered up-regulation of PPARgamma, GFAP and PTEN protein and a reduction of COX-2 protein. However, the effects of CDA-2 on SWO-38 cells could be partly reversed by GW9662, an irreversible PPARgamma antagonist. Our investigation demonstrated that CDA-2 could be a potential drug for tumor differentiation therapy, and activation of the PPARgamma pathway might be a crucial factor in glioma differentiation induced by CDA-2.