Maurocalcine as a non toxic drug carrier overcomes doxorubicin resistance in the cancer cell line MDA-MB 231 Maurocalcine as good doxorubicin delivery vector

• Published in: Pharmaceutical research Vol. 26; no. 4; pp. 836 - 45
• Main Authors: Aroui, Sonia, Ram, Narendra, Appaix, Florence, Ronjat, Michel, Kenani, Abderraouf, Pirollet, Fabienne, de Waard, Michel
• Format: Journal Article
• Language: English
• Published: American Association of Pharmaceutical Scientists 01.04.2009
• Subjects: Biotechnology; Cancer; Cellular Biology; Computer Science; Life Sciences; Drug delivery systems; maurocalcine; doxorubicin; drug resistance; cell-penetrating peptide
• ISSN: 0724-8741; 1573-904X
• DOI: 10.1007/s11095-008-9782-1

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.