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Maurocalcine as a Non Toxic Drug Carrier Overcomes Doxorubicin Resistance in the Cancer Cell Line MDA-MB 231

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Abstract

Purpose

The aim of this study is to overcome tumour cell resistance that generally develops after administration of commonly used anti-cancer drugs, such as doxorubicin.

Methods

Recently, cell penetrating peptides have been used for their ability to deliver non-permeant compounds into cells. One such cell penetrating peptide, maurocalcine, has been isolated from the venom of a Tunisian scorpion. Herein, we report the effects of doxorubicin covalently coupled to an analogue of maurocalcine on drug-sensitive or drug-resistant cell lines MCF7 and MDA-MB 231.

Results

We demonstrated the in vitro anti-tumoral efficacy of the doxorubicin maurocalcine conjugate. On a doxorubicin-sensitive cancer cell line, the maurocalcine-conjugated form appears slightly less efficient than doxorubicin itself. On the contrary, on a doxorubicin-resistant cancer cell line, doxorubicin coupling allows to overcome the drug resistance. This strategy can be generalized to other cell penetrating peptides since Tat and penetratin show similar effects.

Conclusion

We conclude that coupling anti-tumoral drugs to cell penetrating peptides represent a valuable strategy to overcome drug resistance.

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Abbreviations

Con A:

Concanavalin A

CPP:

Cell Penetrating Peptide

Dox:

Doxorubicine

FACS:

Fluorescence Activated Cell Sorting

FITC:

Fluorescein IsoThioCyanate

MCa:

Maurocalcine

MCaAbu :

Maurocalcine analogue with cysteine residues replaced with L-α-aminobutyric acid

MTT:

3-(4, 5-dimethylthiazol-2-yl)-2, 5-diphenyl-tetrazolium bromide

PBS:

Phosphate Buffered Saline

Pen:

Penetratin

RyR1:

Ryanodine Receptor type 1

SMCC:

Succinimidyl 4-[N-Maleimidomethyl]Cyclohexane-1-Carboxylate

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ACKNOWLEDGMENTS

This work was funded by Inserm and a grant from the Life Sciences Division innovation program of the Commissariat à l’Energie Atomique. SA acknowledges the support of the Délégation Générale de la Recherche Scientifique et Technique (Tunisia) and the University of Monastir and University Joseph Fourier for their joint PhD training program.

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Authors and Affiliations

  1. INSERM, U836, Calcium Channels, Functions and Pathologies, BP 170, Grenoble Cedex 9, 38042, France

    Sonia Aroui, Narendra Ram, Florence Appaix, Michel Ronjat, Fabienne Pirollet & Michel De Waard

  2. Université Joseph Fourier, Institut des Neurosciences, BP 170, Grenoble Cedex 9, 38042, France

    Sonia Aroui, Narendra Ram, Florence Appaix, Michel Ronjat, Fabienne Pirollet & Michel De Waard

  3. UR09-09, Molecular Mechanisms and Pathologies, Faculté de Médecine de Monastir, 5019, Monastir, Tunisia

    Sonia Aroui & Abderraouf Kenani

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  1. Sonia Aroui
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  2. Narendra Ram
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  3. Florence Appaix
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  4. Michel Ronjat
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Correspondence to Michel De Waard.

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Aroui, S., Ram, N., Appaix, F. et al. Maurocalcine as a Non Toxic Drug Carrier Overcomes Doxorubicin Resistance in the Cancer Cell Line MDA-MB 231. Pharm Res 26, 836–845 (2009). https://doi.org/10.1007/s11095-008-9782-1

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