title: Hispolon from Phellinus linteus induces apoptosis and sensitizes human cancer cells to the tumor necrosis factor-related apoptosis-inducing ligand through upregulation of death receptors.
abstract: The tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is a potent anticancer agent possessing the ability to induce apoptosis in various cancer cells but not in non‑malignant cells. However, certain type of cancer cells are resistant to TRAIL‑induced apoptosis and some acquire resistance after the first treatment. So development of an agent that can reduce or avoid resistance in TRAIL‑induced apoptosis has garnered significant attention. The present study evaluated the anticancer potential of hispolon in TRAIL‑induced apoptosis and indicated hispolon can sensitize cancer cells to TRAIL. As the mechanism of action was examined, hispolon was found to activate caspase‑3, caspase‑8 and caspase‑9, while downregulating the expression of cell survival proteins such as cFLIP, Bcl‑2 and Bcl‑xL and upregulating the expression of Bax and truncated Bid. We also found hispolon induced death receptors in a non‑cell type‑specific manner. Upregulation of death receptors by hispolon was found to be p53-independent but linked to the induction of CAAT enhancer binding protein homologous protein (CHOP). Overall, hispolon was demonstrated to potentiate the apoptotic effects of TRAIL through downregulation of anti‑apoptotic proteins and upregulation of death receptors linked with CHOP and pERK elevation.
authors.affiliation: Department of Biotechnology, Research Institute (RIBHS) and College of Biomedical and Health Science, Konkuk University, Chungju, Chungbuk 27478, Republic of Korea.
authors.forename: Ji-Hun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Discovery Research Center, C&C Research Laboratories, Suwon‑si, Gyeonggi‑do 440‑746, Republic of Korea.
authors.forename: Yu Chul
authors.initials: YC
authors.lastname: Kim
authors.affiliation: College of Pharmacy, Keimyung University, Dalseo‑Gu, Daegu 704‑701, Republic of Korea.
authors.forename: Byoungduck
authors.initials: B
authors.lastname: Park
mesh_terms: D000972:Antineoplastic Agents, Phytogenic / Q000302:isolation & purification / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051017:Apoptosis Regulatory Proteins / Q000096:biosynthesis* / Q000235:genetics; D022762:CCAAT-Enhancer-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D020169:Caspases / Q000096:biosynthesis* / Q000235:genetics; D002396:Catechols / Q000302:isolation & purification / Q000494:pharmacology*; D045744:Cell Line, Tumor; D015536:Down-Regulation; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D000084682:Phellinus; D010936:Plant Extracts; D011134:Polysaccharides / Q000737:chemistry*; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand / Q000096:biosynthesis* / Q000235:genetics; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D051017:Apoptosis Regulatory Proteins; D022762:CCAAT-Enhancer-Binding Proteins; D002396:Catechols; D009363:Neoplasm Proteins; C526145:Phellinus linteus extract; D010936:Plant Extracts; D011134:Polysaccharides; D053220:Receptors, TNF-Related Apoptosis-Inducing Ligand; D053221:TNF-Related Apoptosis-Inducing Ligand; C105190:TNFRSF10A protein, human; C505653:TNFSF10 protein, human; C103442:hispolon; D020169:Caspases