Selenium-Containing Polysaccharide-Protein Complex in Se-Enriched Ulva fasciata Induces Mitochondria-Mediated Apoptosis in A549 Human Lung Cancer Cells

The role of selenium (Se) and Ulva fasciata as potent cancer chemopreventive and chemotherapeutic agents has been supported by epidemiological, preclinical, and clinical studies. In this study, Se-containing polysaccharide-protein complex (Se-PPC), a novel organoselenium compound, a Se-containing polysaccharide-protein complex in Se-enriched Ulva fasciata, is a potent anti-proliferative agent against human lung cancer A549 cells. Se-PPC markedly inhibited the growth of cancer cells via induction of apoptosis which was accompanied by the formation of apoptotic bodies, an increase in the population of apoptotic sub-G1 phase cells, upregulation of p53, and activation of caspase-3 in A549 cells. Further investigation on intracellular mechanisms indicated that cytochrome C was released from mitochondria into cytosol in A549 cells after Se-PPC treatment. Se-PPC induced depletion of mitochondrial membrane potential (Delta Psi m) in A549 cells through regulating the expression of anti-apoptotic (Bcl-2, Bcl-XL) and pro-apoptotic (Bax, Bid) proteins, resulting in disruption of the activation of caspase-9. This is the first report to demonstrate the cytotoxic effect of Se-PPC on human cancer cells and to provide a possible mechanism for this activity. Thus, Se-PPC is a promising novel organoselenium compound with potential to treat human cancers.