title: Ganoderma lucidum polysaccharides target a Fas/caspase dependent pathway to induce apoptosis in human colon cancer cells.
abstract: Ganoderma lucidum polysaccharides (GLP) extracted from Ganoderma lucidum have been shown to induce cell death in some kinds of cancer cells. This study investigated the cytotoxic and apoptotic effect of GLP on HCT-116 human colon cancer cells and the molecular mechanisms involved. Cell proliferation, cell migration, lactate dehydrogenase (LDH) levels and intracellular free calcium levels ([Ca(2+)]i) were determined by MTT, wound-healing, LDH release and fluorescence assays, respectively. Cell apoptosis was observed by scanning and transmission electron microscopy. For the mechanism studies, caspase-8 activation, and Fas and caspase-3 expression were evaluated. Treatment of HCT-116 cells with various concentrations of GLP (0.625-5 mg/mL) resulted in a significant decrease in cell viability (P< 0.01). This study showed that the antitumor activity of GLP was related to cell migration inhibition, cell morphology changes, intracellular Ca(2+) elevation and LDH release. Also, increase in the levels of caspase-8 activity was involved in GLP-induced apoptosis. Western blotting indicated that Fas and caspase-3 protein expression was up-regulated after exposure to GLP. This investigation demonstrated for the first time that GLP shows prominent anticancer activities against the HCT-116 human colon cancer cell line through triggering intracellular calcium release and the death receptor pathway.
authors.affiliation: Hunan Provincial Key Laboratory of Crop Germplasm Innovation and Utilization, Hunan Agricultural University, Changsha, China E-mail : xiongxingyao@126.com; 409600160@qq.com.
authors.forename: Zengenni
authors.initials: Z
authors.lastname: Liang
authors.forename: Yu-Tong
authors.initials: YT
authors.lastname: Guo
authors.forename: You-Jin
authors.initials: YJ
authors.lastname: Yi
authors.forename: Ren-Cai
authors.initials: RC
authors.lastname: Wang
authors.forename: Qiu-Long
authors.initials: QL
authors.lastname: Hu
authors.forename: Xing-Yao
authors.initials: XY
authors.lastname: Xiong
mesh_terms: D017209:Apoptosis / Q000187:drug effects*; D002118:Calcium / Q000032:analysis; D053148:Caspase 3 / Q000378:metabolism*; D053181:Caspase 8 / Q000378:metabolism; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D003110:Colonic Neoplasms / Q000188:drug therapy*; D053200:Fas-Associated Death Domain Protein / Q000378:metabolism*; D062610:Fungal Polysaccharides / Q000009:adverse effects / Q000494:pharmacology*; D045325:HCT116 Cells; D006801:Humans; D007770:L-Lactate Dehydrogenase / Q000096:biosynthesis; D008297:Male; D046529:Microscopy, Electron, Transmission; D020940:Reishi; D015398:Signal Transduction / Q000187:drug effects
chemical_list: D053200:Fas-Associated Death Domain Protein; D062610:Fungal Polysaccharides; D007770:L-Lactate Dehydrogenase; D053148:Caspase 3; D053181:Caspase 8; D002118:Calcium