title: Sialic acid-binding lectin (leczyme) induces apoptosis to malignant mesothelioma and exerts synergistic antitumor effects with TRAIL.
abstract: Malignant mesothelioma is a highly aggressive tumor with poor prognosis. An effective drug for treatment of malignant mesothelioma is greatly needed. Sialic acid-binding lectin (SBL) isolated from oocytes of Rana catesbeiana is a multifunctional protein which has lectin activity, ribonuclease activity and antitumor activity, so it could be developed as a new type of anticancer drug. The validity of SBL for treatment of malignant mesothelioma was assessed using three malignant mesotheliomas and a non-malignant mesothlial cell line. Effectiveness of combinatorial treatment of SBL and tumor necrosis factor-related apoptosis inducing ligand (TRAIL) was also elucidated and characterized. SBL induced tumor-selective cytotoxicity that was attributed to induction of apoptosis. Combinatorial treatment of SBL and TRAIL showed synergistic apoptosis-inducing effect. Additional experiments revealed that Bid was the mediating molecule for the synergistic effect in SBL and TRAIL. These results suggested that SBL could be a promising candidate for the therapeutics for malignant mesothelioma. Furthermore, the combinatorial treatment of SBL and TRAIL could be an effective regimen against malignant mesothelioma.
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Takeo
authors.initials: T
authors.lastname: Tatsuta
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hosono
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Kohta
authors.initials: K
authors.lastname: Takahashi
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Takashi
authors.initials: T
authors.lastname: Omoto
authors.affiliation: Fukushima Medical University, Fukushima 960-1295, Japan.
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Kariya
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Division of Biomembrane Research, Pacific Northwest Research Institute, WA 98122, USA.
authors.forename: Senitiroh
authors.initials: S
authors.lastname: Hakomori
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, Aoba-ku, Sendai 981-8558, Japan.
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nitta
mesh_terms: D029845:Amphibian Proteins / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051023:BH3 Interacting Domain Death Agonist Protein / Q000378:metabolism; D015153:Blotting, Western; D049109:Cell Proliferation; D004338:Drug Combinations; D004357:Drug Synergism; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D008175:Lung Neoplasms / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D053078:Membrane Potential, Mitochondrial; D008654:Mesothelioma / Q000378:metabolism / Q000473:pathology* / Q000517:prevention & control; D000086002:Mesothelioma, Malignant; D008928:Mitochondria / Q000378:metabolism; D012260:Ribonucleases / Q000494:pharmacology*; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology*; D014407:Tumor Cells, Cultured
chemical_list: D029845:Amphibian Proteins; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D004338:Drug Combinations; D037102:Lectins; D053221:TNF-Related Apoptosis-Inducing Ligand; D012260:Ribonucleases; C448662:leczyme protein, Rana