Antineoplastic effects of deoxypodophyllotoxin,a potent cytotoxic agent of plant origin,on glioblastoma U-87 MG and SF126 cells

Background: deoxypodophyllotoxin (dpt) is a semi-synthetic compound derived from the extract of dysosma versipellis (hance) m. cheng,one of the most popular chinese herbal medicines. the present study evaluates the in vitro cytotoxicity of dpt on a wide panel of human cancer cell lines and investigates its molecular mechanism of action on high grade glioma u-87 mg and sf126 cells. methods: the growth inhibitory effect of dpt on different types of human cancer cells was measured by the cell counting kit-8 (cck-8) assay. for the elucidation of the nature of the cellular response to dpt-treatment; flow cytometry-based assays,light and fluorescent microscopy,caspase colorimetric and inhibition assays,and western blot analysis were performed. results: our data show that dpt possesses a potent growth-inhibitory action,with ic50 values in nanomolar ranges. cell cycle analysis revealed g2/m phase arrest in a dose- and time-dependent manner before cell death occurred. additional studies indicated that dpt induced g2 arrest in u-87 mg cells by decreasing the expression of cdc2,cyclin b1,and cdc25c proteins. in contrast,dpt failed to downregulate these cell cycle regulatory molecules in sf126 glioblastoma cells and stopped the cell cycle at m phase. interestingly,morphological changes and biochemical markers such as phosphatydylserine externalization,dna fragmentation,and caspase activation,confirmed that dpt-treatment resulted in an induction of apoptosis in both examined cell lines via caspase-dependent pathways. conclusions: taken together,our data demonstrated that dpt possesses a potent in vitro cytotoxic activity and exerts its effect via g2/m arrest and apoptosis. © 2014 institute of pharmacology,polish academy of sciences. published by elsevier urban & partner sp. z o.o. all rights reserved.