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Updated: Jul 31, 2026

Detection of Toxin Translocation into the Host Cytosol by Surface Plasmon Resonance
Published on: January 3, 2012
Preclinical pharmacology of cholera toxin
J M Reid1, J W Benson, J Viallet
1Department of Oncology, Research, Mayo Clinic and Foundation, Rochester, MN 55905, USA.
Abstract:
Cholera toxin was selected for pharmacologic evaluation by the National Cancer Institute on the basis of antiproliferative activity against small-cell and non-small-cell lung-cancer cell lines. A feature common to the sensitive cell lines was abundant expression of GM1 ganglioside, the cellular receptor for cholera toxin. A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantitate cholera toxin in biological fluids. A sigmoidal relationship was observed between the cholera toxin plasma concentration and the absorbance at 490 nm (OD490) of the product of horseradish peroxidase-catalyzed oxidation of o-phenylenediamine over the range of 6.25-1,600 ng/ml. Logit transformation of the OD490 data was linear over the entire concentration range and assay variability was less than 25%. Cholera toxin was stable in murine and human whole blood and plasma. Following i.v. administration of 1,500 micrograms/kg to male CD2F1 mice, cholera toxin plasma elimination was described by a two-compartment open model. The half-lives (t1/2 alpha, t1/2 beta), plasma clearance, and steady-state volume of distribution were 0.7 min, 49 min, 24 ml min-1 kg-1 912 ml/kg, respectively. Cholera toxin was not detected in plasma following an s.c. dose of 1,500 micrograms/kg. Urinary recovery following intravenous drug administration was less than 0.1%.
Insights
Cholera toxin exhibits antiproliferative effects against lung cancer cells expressing GM1 ganglioside. Pharmacokinetic studies revealed rapid plasma elimination after intravenous administration in mice.
Area of Science:
- Pharmacology
- Oncology
- Biochemistry
Background:
- Cholera toxin demonstrates antiproliferative activity against lung cancer cell lines.
- Sensitive cell lines overexpress GM1 ganglioside, the cellular receptor for cholera toxin.
Purpose of the Study:
- To evaluate cholera toxin for pharmacologic use in cancer treatment.
- To develop a method for quantifying cholera toxin in biological fluids.
- To characterize the pharmacokinetics of cholera toxin in mice.
Main Methods:
- A sandwich enzyme-linked immunosorbent assay (ELISA) was developed to quantify cholera toxin.
- ELISA linearity and variability were assessed using logit transformation.
- Pharmacokinetic parameters were determined after intravenous and subcutaneous administration in mice.
Main Results:
- The ELISA demonstrated a sigmoidal relationship between cholera toxin concentration and absorbance, with low variability (<25%).
- Cholera toxin was stable in blood and plasma.
- Following IV administration, cholera toxin exhibited rapid plasma elimination (t1/2 beta = 49 min) and low bioavailability via SC route.
Conclusions:
- Cholera toxin's antiproliferative properties and specific receptor binding warrant further investigation for lung cancer therapy.
- The developed ELISA is a reliable tool for quantifying cholera toxin in biological samples.
- Understanding cholera toxin's pharmacokinetic profile is crucial for its potential therapeutic applications.
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