Jiménez-Medina, EvaBerruguilla, EnriqueRomero, IreneAlgarra, IgnacioCollado, AntoniaGarrido, FedericoGarcia-Lora, Angel2012-11-222012-11-222008-03-24Jiménez-Medina E, Berruguilla E, Romero R ,Algarra I, Collado A, Garrido F.The immunomodulator PSK induces in vitro cytotoxic activity in tumour cell lines via arrest of cell cycle and induction of apoptosis.BMC Cancer. 2008 Mar 24;8:78http://hdl.handle.net/10668/644Journal Article; Research Support, Non-U.S. Gov't;BACKGROUND Protein-bound polysaccharide (PSK) is derived from the CM-101 strain of the fungus Coriolus versicolor and has shown anticancer activity in vitro and in in vivo experimental models and human cancers. Several randomized clinical trials have demonstrated that PSK has great potential in adjuvant cancer therapy, with positive results in the adjuvant treatment of gastric, esophageal, colorectal, breast and lung cancers. These studies have suggested the efficacy of PSK as an immunomodulator of biological responses. The precise molecular mechanisms responsible for its biological activity have yet to be fully elucidated. METHODS The in vitro cytotoxic anti-tumour activity of PSK has been evaluated in various tumour cell lines derived from leukaemias, melanomas, fibrosarcomas and cervix, lung, pancreas and gastric cancers. Tumour cell proliferation in vitro was measured by BrdU incorporation and viable cell count. Effect of PSK on human peripheral blood lymphocyte (PBL) proliferation in vitro was also analyzed. Studies of cell cycle and apoptosis were performed in PSK-treated cells. RESULTS PSK showed in vitro inhibition of tumour cell proliferation as measured by BrdU incorporation and viable cell count. The inhibition ranged from 22 to 84%. Inhibition mechanisms were identified as cell cycle arrest, with cell accumulation in G0/G1 phase and increase in apoptosis and caspase-3 expression. These results indicate that PSK has a direct cytotoxic activity in vitro, inhibiting tumour cell proliferation. In contrast, PSK shows a synergistic effect with IL-2 that increases PBL proliferation. CONCLUSION These results indicate that PSK has cytotoxic activity in vitro on tumour cell lines. This new cytotoxic activity of PSK on tumour cells is independent of its previously described immunomodulatory activity on NK cells.enAnimalesApoptosisCiclo CelularLínea CelularProliferación de la CélulaEnsayos de Selección de Medicamentos AntitumoralesProteínas FúngicasHongosCélulas HeLaHumanosFactores InmunológicosCélulas JurkatLinfocitosMelanoma ExperimentalRatonesPolisacáridosProteoglicanosMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Death::ApoptosisMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell CycleMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, TumorMedical Subject Headings::Phenomena and Processes::Cell Physiological Phenomena::Cell Physiological Processes::Cell Growth Processes::Cell ProliferationMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Diagnosis::Diagnostic Techniques and Procedures::Clinical Laboratory Techniques::Cytological Techniques::Drug Screening Assays, AntitumorMedical Subject Headings::Chemicals and Drugs::Amino Acids, Peptides, and Proteins::Proteins::Fungal ProteinsMedical Subject Headings::Organisms::Eukaryota::FungiMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::HeLa CellsMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Primates::Haplorhini::Catarrhini::Hominidae::HumansMedical Subject Headings::Chemicals and Drugs::Chemical Actions and Uses::Pharmacologic Actions::Physiological Effects of Drugs::Immunologic FactorsMedical Subject Headings::Anatomy::Cells::Cells, Cultured::Cell Line::Cell Line, Tumor::Jurkat CellsMedical Subject Headings::Anatomy::Cells::Blood Cells::Leukocytes::Leukocytes, Mononuclear::LymphocytesMedical Subject Headings::Analytical, Diagnostic and Therapeutic Techniques and Equipment::Investigative Techniques::Models, Animal::Disease Models, Animal::Neoplasms, Experimental::Melanoma, ExperimentalMedical Subject Headings::Organisms::Eukaryota::Animals::Chordata::Vertebrates::Mammals::Rodentia::Muridae::Murinae::MiceMedical Subject Headings::Chemicals and Drugs::Carbohydrates::PolysaccharidesMedical Subject Headings::Chemicals and Drugs::Carbohydrates::Polysaccharides::Proteoglycansresearch article18366723open access10.1186/1471-2407-8-781471-2407PMC2291471