Toxins 2010, 2(10), 2467-2477; doi:10.3390/toxins2102467
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Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy

1 Department of Medical Biosciences, Umeå University, S-901 85 Umea, Sweden 2 Department of Odontology, Umeå University, S-901 85 Umea, Sweden
* Author to whom correspondence should be addressed.
Received: 19 September 2010; in revised form: 15 October 2010 / Accepted: 19 October 2010 / Published: 25 October 2010
(This article belongs to the Special Issue Toxins as Therapeutics)
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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.
Keywords: apoptosis; cancer; Gb3; verotoxin-1; multi-drug resistance; MDR1; P-gp

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MDPI and ACS Style

Behnam-Motlagh, P.; Tyler, A.; Grankvist, K.; Johansson, A. Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy. Toxins 2010, 2, 2467-2477.

AMA Style

Behnam-Motlagh P, Tyler A, Grankvist K, Johansson A. Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy. Toxins. 2010; 2(10):2467-2477.

Chicago/Turabian Style

Behnam-Motlagh, Parviz; Tyler, Andreas; Grankvist, Kjell; Johansson, Anders. 2010. "Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy." Toxins 2, no. 10: 2467-2477.

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