Toxins 2010, 2(10), 2467-2477; doi:10.3390/toxins2102467
Review

Verotoxin-1 Treatment or Manipulation of its Receptor Globotriaosylceramide (Gb3) for Reversal of Multidrug Resistance to Cancer Chemotherapy

1email, 1email, 1email and 2,* email
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)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
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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