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Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Medical Biosciences, Clinical chemistry.
Umeå University, Faculty of Medicine, Department of Odontology. (Aa-gruppen)
2010 (English)In: Toxins, ISSN 2072-6651, Vol. 2, no 10, 2467-2477 p.Article, review/survey (Refereed) Published
Abstract [en]

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.

Place, publisher, year, edition, pages
Basel: MDPI , 2010. Vol. 2, no 10, 2467-2477 p.
Keyword [en]
apoptosis, cancer, Gb3, verotoxin-1, multi-drug resistance, MDR1, P-gp
National Category
Cancer and Oncology
Research subject
cellforskning
Identifiers
URN: urn:nbn:se:umu:diva-40654DOI: 10.3390/toxins2102467ISI: 000208435600007OAI: oai:DiVA.org:umu-40654DiVA: diva2:401769
Available from: 2011-03-07 Created: 2011-03-03 Last updated: 2011-09-02Bibliographically approved

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Behnam-Motlagh, ParvizTyler, AndreasGrankvist, KjellJohansson, Anders
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Clinical chemistryDepartment of Odontology
Cancer and Oncology

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