Crude extract of Euphorbia formosana induces apoptosis of DU145 human prostate cancer cells acts through the caspase-dependent and independent signaling pathway.

Prostate cancer is the most frequently diagnosed malignancy in men and the second highest contributor of male cancer mortality. The crude extract of Euphorbia formosana (CEEF) has been used for treatment of different diseases but the cytotoxic effects of CEEF on human cancer cells have not been reported. The purpose of the present experiments was to determine effects of CEEF on cell cycle distribution and induction of apoptosis in DU145 human prostate cancer cells in vitro. Contrast-phase microscope was used for examining cell morphological changes. Flow cytometric assays were used for cell viability, cell cycle, apoptosis, reactive oxygen species, and Ca2+ production and mitochondria membrane potential (ΔΨm ). Western blotting was used for examining protein expression of cell cycle and apoptosis associated proteins. Real-time PCR was used for examining mRNA levels of caspase-3, -8, and -9, AIF, and Endo G. Confocal laser microscope was used to examine the translocation of AIF, Endo G, and cytochrome in DU145 cells after CEEF exposure. CEEF-induced cell morphological changes, decreased the percentage of viable cells, and induced S phase arrest and apoptosis in DU145 cells. Furthermore, CEEF promoted RAS and Ca2+ production and reduced ΔΨm levels. Real-time QPCR confirmed that CEEF promoted the mRNA expression of caspase-3 and -9, AIF and Endo G and we found that AIF and Endo G and cytochrome c were released from mitochondria. Taken together, CEEF-induced cytotoxic effects via ROS production, induced S phase arrest and induction of apoptosis through caspase-dependent and independent and mitochondria-dependent pathways in DU245 cancer cells. © 2015 Wiley Periodicals, Inc. Environ Toxicol 31: 1600-1611, 2016.

Crude extract of Euphorbia formosana inhibits the migration and invasion of DU145 human prostate cancer cells: The role of matrix metalloproteinase-2/9 inhibition via the MAPK signaling pathway.

Prostate cancer is a common worldwide health problem in males with a poor prognosis due in part to tumor invasion and migration. The crude extract of Euphorbia formosana (CEEF) has been used for the treatment of numerous diseases, however, its effects on the migration and invasion of prostate cancer cells have yet to be examined. In the present study, we investigated the effects of CEEF on the migration and invasion of DU145 human prostate cancer cells in vitro. The wound healing assay and the Matrigel-uncoated migration assay were used to examine the migration of cancer cells. Western blotting was used to examine the levels of proteins associated with migration and invasion, and gelatin zymography was used to examine the secretion levels of matrix metalloproteinases-2 and -9 (MMP­2/9) from DU145 cells following exposure to CEEF. The results indicated that CEEF suppressed the migration and invasion of DU145 prostate cancer cells and that these effects are exerted in a concentration- and time-dependent manner. CEEF inhibited the ERK1/2, p38, JNK, SOS1, PKC, PI3K and MMP-2/9 protein expression in DU145 cells. The results demonstrated that CEEF suppressed the migration and invasion of DU145 cells through inhibition of the mitogen-activated protein kinase (MAPK) signaling pathway resulting in the inhibition of MMP-2/9 in DU145 human prostate cancer cells.