title: MRP1 expressed on Burkitt's lymphoma cells was depleted by catfish egg lectin through Gb3-glycosphingolipid and enhanced cytotoxic effect of drugs.
abstract: A novel anticancer mechanism of catfish (Silurus asotus) egg lectin (SAL) was found to occur via the down-regulation of the membrane transopter protein, MRP1 (multidrug resistance associate protein-1) on Burkitt's lymphoma cells through Gb3(Galα1-4Galβ1-4Glc)-glycosphingolipid. Although SAL did not influence the viability of the cells directly, only 10 and 100 ng/mL of vincristine and etoposide, respectively induced anticancer effects when the lectin was applied in conjunction with these drugs. These phenomena were specifically inhibited by the co-presence of the α-galactoside, melibiose, which is a strong haptenic sugar of SAL that mimicks Gb3. The degree of expression regulation of the transporter proteins on the cells surface was investigated through the examination of the binding between SAL and Gb3-glycosphingolipid by immunological and molecular biological procedures. PCR data showed that MRP1 was more highly expressed when compared to another ATP-binding cassette family, multi-drug resistant protein and the expression levels of MRP1 on the cells were specifically dose- and time-dependently depleted by the addition of SAL. These results were also evaluated by immunological procedures using FACS and western-blotting. Small interfering RNA coding a part of MRP1 was transfected to Raji cells to knock down the protein, and cell death was increased by 10% when vincristine was administered at a concentration as low as 10 ng/mL compared to non-transfected cells. These results indicated that SAL possesses the potential to enhance the anticancer activites of low-concentrations of vincristine by the down-regulating the MRP1 gene expression to inhibit the multidrug resistance by binding to the target ligand Gb3-glycosphingolipid on Burkitt's lymphoma cells.
authors.affiliation: Division of Cell Recognition Study, Institute of Molecular Biomembrane and Glycobiology, Tohoku Pharmaceutical University, 4-4-1 Komatsushima, Aoba-Ku, Sendai, 981-8558, Japan. yukifujii2010@gmail.com
authors.forename: Yuki
authors.initials: Y
authors.lastname: Fujii
authors.forename: Shigeki
authors.initials: S
authors.lastname: Sugawara
authors.forename: Daisuke
authors.initials: D
authors.lastname: Araki
authors.forename: Tasuku
authors.initials: T
authors.lastname: Kawano
authors.forename: Takeo
authors.initials: T
authors.lastname: Tatsuta
authors.forename: Kohta
authors.initials: K
authors.lastname: Takahashi
authors.forename: Sarkar M A
authors.initials: SM
authors.lastname: Kawsar
authors.forename: Ryo
authors.initials: R
authors.lastname: Matsumoto
authors.forename: Robert A
authors.initials: RA
authors.lastname: Kanaly
authors.forename: Hidetaro
authors.initials: H
authors.lastname: Yasumitsu
authors.forename: Yasuhiro
authors.initials: Y
authors.lastname: Ozeki
authors.forename: Masahiro
authors.initials: M
authors.lastname: Hosono
authors.forename: Taeko
authors.initials: T
authors.lastname: Miyagi
authors.forename: Sen-Itiroh
authors.initials: SI
authors.lastname: Hakomori
authors.forename: Motoaki
authors.initials: M
authors.lastname: Takayanagi
authors.forename: Kazuo
authors.initials: K
authors.lastname: Nitta
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D002051:Burkitt Lymphoma / Q000188:drug therapy / Q000235:genetics / Q000378:metabolism*; D002397:Catfishes / Q000378:metabolism*; D045744:Cell Line, Tumor; D005047:Etoposide / Q000494:pharmacology; D029941:Fish Proteins / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D037102:Lectins / Q000494:pharmacology*; D027425:ATP-Binding Cassette, Sub-Family C Proteins / Q000235:genetics / Q000378:metabolism*; D010063:Ovum / Q000737:chemistry* / Q000378:metabolism; D011485:Protein Binding / Q000187:drug effects; D014312:Trisaccharides / Q000378:metabolism*; D014750:Vincristine / Q000494:pharmacology
chemical_list: D000970:Antineoplastic Agents; D005047:Etoposide; D029941:Fish Proteins; D006028:Glycosphingolipids; D037102:Lectins; D027425:ATP-Binding Cassette, Sub-Family C Proteins; D014312:Trisaccharides; D014750:Vincristine; C402295:rhamnose-binding lectin, catfish; C113460:globotriose; C421109:multidrug resistance-associated protein 1
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