title: Internalization of a novel, huge lectin from Ibacus novemdentatus (slipper lobster) induces apoptosis of mammalian cancer cells.
abstract: An N-acetyl sugar-binding lectin (termed iNoL) displaying cytotoxic activity against human cancer cells was isolated from the slipper lobster Ibacus novemdentatus (family Scyllaridae). iNoL recognized monosaccharides containing N-acetyl group, and glycoproteins (e.g., BSM) containing oligosaccharides with N-acetyl sugar. iNoL was composed of five subunits (330, 260, 200, 140, and 30 kDa), which in turn consisted of 70-, 40-, and 30-kDa polypeptides held together by disulfide bonds. Electron microscopic observations and gel permeation chromatography indicated that iNoL was a huge (500-kDa) molecule and had a polygonal structure under physiological conditions. iNoL displayed cytotoxic (apoptotic) effects against human cancer cell lines MCF7 and T47D (breast), HeLa (ovarian), and Caco2 (colonic), through incorporation (internalization) into cells. The lectin was transported into lysosomes via endosomes. Its cytotoxic effect and incorporation into cells were inhibited by the co-presence of N-acetyl-D-mannosamine (ManNAc). Treatment of HeLa cells with iNoL resulted in DNA fragmentation and chromatin condensation, through activation of caspase-9 and -3. In summary, the novel crustacean lectin iNoL is incorporated into mammalian cancer cells through glycoconjugate interaction, and has cytotoxic (apoptotic) effects.
authors.affiliation: Department of Pharmacy, Graduate School of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki, 859-3298, Japan. yfujii@niu.ac.jp.
authors.forename: Y
authors.initials: Y
authors.lastname: Fujii
authors.affiliation: Department of Pharmacy, Graduate School of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki, 859-3298, Japan.
authors.forename: T
authors.initials: T
authors.lastname: Fujiwara
authors.affiliation: Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Koide
authors.affiliation: Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.|Department of Biochemistry and Molecular Biology, Faculty of Science, University of Rajshahi, Rajshahi, -6205, Bangladesh.
authors.forename: I
authors.initials: I
authors.lastname: Hasan
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Medical & Pharmaceutical University, 4-4-1 Komatsushima, Aoba-ku, Sendai, 981-8558, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Sugawara
authors.affiliation: Department of Natural Sciences, Varendra University, Rajshahi, -6204, Bangladesh.
authors.forename: S
authors.initials: S
authors.lastname: Rajia
authors.affiliation: Department of Chemistry, Faculty of Sciences, University of Chittagong, Chittagong, -4331, Bangladesh.
authors.forename: S M A
authors.initials: SM
authors.lastname: Kawsar
authors.affiliation: Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Yamamoto
authors.affiliation: Department of Pharmacy, Yoshikawa Central General Hospital, 111 Hiranuma, Yoshikawa, Saitama, 342-0056, Japan.
authors.forename: D
authors.initials: D
authors.lastname: Araki
authors.affiliation: Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
authors.forename: R A
authors.initials: RA
authors.lastname: Kanaly
authors.affiliation: Department of Pharmacy, Graduate School of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki, 859-3298, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ogawa
authors.affiliation: Department of Pharmacy, Graduate School of Pharmaceutical Science, Nagasaki International University, 2825-7 Huis Ten Bosch, Sasebo, Nagasaki, 859-3298, Japan.
authors.forename: H
authors.initials: H
authors.lastname: Fujita
authors.affiliation: Department of Life and Environmental System Science, Graduate School of NanoBio Sciences, Yokohama City University, 22-2 Seto, Kanazawa-ku, Yokohama, 236-0027, Japan.
authors.forename: Y
authors.initials: Y
authors.lastname: Ozeki
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D018938:Caco-2 Cells; D053148:Caspase 3 / Q000378:metabolism; D053453:Caspase 9 / Q000378:metabolism; D033364:Decapoda / Q000737:chemistry*; D004705:Endocytosis; D011992:Endosomes / Q000187:drug effects / Q000378:metabolism; D006023:Glycoproteins / Q000378:metabolism; D006367:HeLa Cells; D006801:Humans; D037102:Lectins / Q000737:chemistry / Q000494:pharmacology* / Q000633:toxicity; D008247:Lysosomes / Q000187:drug effects / Q000378:metabolism; D061986:MCF-7 Cells; D011485:Protein Binding
chemical_list: D000970:Antineoplastic Agents; D006023:Glycoproteins; D037102:Lectins; D053148:Caspase 3; D053453:Caspase 9
keywords: Apoptosis; Caspase; Endocytosis; Hemolymph; Lobster; N-acetyl sugar