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

• Published in: Marine drugs 2017-07, Vol.15 (7), p.215
• Main Authors: Sun, Xian, Zhong, Yu, Luo, Hongtian, Yang, Yufeng
• Format: Article
• Language: English
• Subjects: A549 Cells; Activation; Antineoplastic Agents - pharmacology; Apoptosis; Apoptosis - drug effects; BAX protein; Bcl-2 protein; Bcl-x protein; Cancer; Caspase; Caspase 3 - metabolism; Caspase 9 - metabolism; Caspase-3; Caspase-9; Cell Line, Tumor; Cell Proliferation - drug effects; Cells; Chemotherapy; Cytochrome c; Cytochromes; Cytochromes c - metabolism; Cytosol; Cytotoxicity; Epidemiology; G1 phase; G1 Phase - drug effects; Humans; Lung cancer; Lungs; Membrane potential; Membrane Potential, Mitochondrial - drug effects; Mitochondria; Mitochondria - drug effects; Organoplatinum Compounds - pharmacology; Organoselenium compounds; p53 Protein; Polysaccharides; Polysaccharides - pharmacology; Proteins; reactive oxygen species; Selenium; Selenium - pharmacology; selenium-containing polysaccharide-protein complex; Signal Transduction - drug effects; Tumor Suppressor Protein p53 - metabolism; Ulva - metabolism; Ulva fasciata; Up-Regulation - drug effects
• ISSN: 1660-3397; 1660-3397
• DOI: 10.3390/md15070215

The role of selenium (Se) and 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 , 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 (Δ ) 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.