Cytotoxic Effect of Chloroform Extract of Portulaca oleracea by Inducing Apoptosis and Suppressing Expression of Stemness Regulators in Human Glioblastoma Stem Cells

Abstract

Glioblastoma stem cells (GSCs) are a major cause of tumor initiation, metastasis, chemoresistance, and recurrence in glioblastoma. Therefore, eradicating GSCs is a powerful strategy for the effective treatment of glioblastoma. Portulaca oleracea, an edible leaf vegetable, has been used in traditional medicine to treat a variety of diseases in Asia, Africa, and Europe. In this study, we evaluated the cytotoxic activity of ethanol, ethyl acetate, and chloroform extracts of P. oleracea (EEPO, EAEPO, and CEPO) against U87MG- and U373MG-derived GSCs. The results showed that CEPO most potently inhibited the proliferation and tumorsphere formation in both GSCs. Furthermore, CEPO promoted apoptosis in U87MG- and U373MG-derived GSCs through induction of nuclear fragmentation, loss of mitochondrial membrane potential, increase of reactive oxygen species, and caspase cascade activation. In addition, CEPO downregulated the expression of key cancer stemness regulators, including Sox-2, Oct-4, and STAT3 in both GSCs. CEPO also suppressed in vivo tumor growth of U87MG-derived GSCs in a chick embryo chorioallantoic membrane model. Therefore, CEPO could be potentially used as a natural medicine for the prevention and treatment of glioblastoma by eliminating GSCs.