title: Verotoxin-1 treatment or manipulation of its receptor globotriaosylceramide (gb3) for reversal of multidrug resistance to cancer chemotherapy.
abstract: A major problem with anti-cancer drug treatment is the development of acquired multidrug resistance (MDR) of the tumor cells. Verotoxin-1 (VT-1) exerts its cytotoxicity by targeting the globotriaosylceramide membrane receptor (Gb3), a glycolipid associated with multidrug resistance. Gb3 is overexpressed in many human tumors and tumor cell lines with inherent or acquired MDR. Gb3 is co-expressed and interplays with the membrane efflux transporter P-gp encoded by the MDR1 gene. P-gp could act as a lipid flippase and stimulate Gb3 induction when tumor cells are exposed to cancer chemotherapy. Recent work has shown that apoptosis and inherent or acquired multidrug resistance in Gb3-expressing tumors could be affected by VT-1 holotoxin, a sub-toxic concentration of the holotoxin concomitant with chemotherapy or its Gb3-binding B-subunit coupled to cytotoxic or immunomodulatory drug, as well as chemical manipulation of Gb3 expression. The interplay between Gb3 and P-gp thus gives a possible physiological approach to augment the chemotherapeutic effect in multidrug resistant tumors.
authors: Department of Medical Biosciences, Umeå University, S-901 85 Umea, Sweden. parviz.behnam@medbio.umu.se
authors: Parviz
authors: P
authors: Behnam-Motlagh
authors: Andreas
authors: A
authors: Tyler
authors: Kjell
authors: K
authors: Grankvist
authors: Anders
authors: A
authors: Johansson
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000818:Animals; D018432:Drug Resistance, Multiple; D019008:Drug Resistance, Neoplasm; D006028:Glycosphingolipids / Q000378:metabolism*; D006801:Humans; D009369:Neoplasms / Q000188:drug therapy; D022622:Shiga Toxin 1 / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D006028:Glycosphingolipids; D022622:Shiga Toxin 1