Abstract
Latex of Euphorbia antiquorum (EA) has inhibitory effects on several different cancer cell lines. However, the molecular mechanism of EA inhibitory effects on human cervical cancer HeLa cell growth has not been explored. EA induced apoptosis, which was characterized by morphological change, DNA fragmentation, increased sub-G1 population, and alterations in levels of apoptosis-associated proteins. Treatment with EA increased cell death and expression levels of caspase-8, -9, and -3. EA suppressed expression of Bcl-2, increased Bax, and reduced cleavage of Bid and the translocation of tBid to the mitochondria and the release of cytochrome c from mitochondria. EA caused a loss of mitochondrial membrane potential (ΔΨm) and an increase in cellular reactive oxygen species (ROS). EA-induced ROS formation was suppressed by cyclosporine A (an inhibitor of the ΔΨm) or allopurinol (an effective scavenger of ROS). EA also increased expression of Fas, FasL, and c-Jun N-terminal kinase (JNK), p38, and mitogen-activated protein kinase (MAPK) and decreased expression of extracellular signal-regulated kinase (ERK) 1/2-p. Co-treatment with the JNK inhibitor SP600125 inhibited EA-induced apoptosis and the activation of caspase-8, -9, and -3. Results of this study provide support for the hypothesis that EA causes cell death via apoptotic pathways in human cervical adenocarcinoma HeLa cells.