Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy
2010 (English)In: Toxins, ISSN 2072-6651, Vol. 2, no 10, 2467-2477 p.Article, review/survey (Refereed) Published
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.
apoptosis, cancer, Gb3, verotoxin-1, multi-drug resistance, MDR1, P-gp
Cancer and Oncology
Research subject cellforskning
IdentifiersURN: urn:nbn:se:umu:diva-40654DOI: 10.3390/toxins2102467ISI: 000208435600007OAI: oai:DiVA.org:umu-40654DiVA: diva2:401769