Effects of self-assembled cell-penetrating peptides and their nano-complexes on ABCB۱ expression and activity

Publish Year: 1400
نوع سند: مقاله ژورنالی
زبان: English
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JR_IJBMS-24-3_014

تاریخ نمایه سازی: 6 اردیبهشت 1400

Abstract:

Objective(s): Doxorubicin (Dox) is one of the most well-known chemotherapeutics that are commonly applied for a wide range of cancer treatments. However, in most cases, efflux pumps like P-glycoprotein (P-gp), expel the taken drugs out of the cell and decrease the Dox bioavailability. Expression of P-gp is associated with elevated mRNA expression of the ATP-binding cassette B۱ (ABCB۱) gene. Materials and Methods: In the current study, different sequences of cell-penetrating peptides (CPPs) containing tryptophan, lysine, and arginine and their nano-complexes were synthesized and their impact on the expression and activity of the ABCB۱ gene was evaluated in the A۵۴۹ lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A۵۴۹ cell line was assessed. Results: The designed peptides, including [W۴K۴], [WR]۳-QGR, R۱۰, and K۱۰ increased Dox cytotoxicity after ۴۸ hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin۱۲۳ accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB۱ gene expression, of which, [W۴K۴] resulted in the lowest expression ratio. Conclusion: [W۴K۴], [WR]۳-QGR, R۱۰, and K۱۰ could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.

Keywords:

Cancer therapy CPPs Doxorubicin Multi , drug resistance P , gp

Authors

Mehri Niazi

Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Parvin Zakeri-Milani

Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Mehdi Soleymani-Goloujeh

Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran

Ali Mohammadi

Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

Muhammad Sarfraz

College of Pharmacy, Al Ain University of Science and Technology, Al Ain ۶۴۱۴۱, UAE

Raimar Löbenberg

Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, T۶G ۲H۵, Canada

saeedeh Najafi-Hajivar

Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Javid Shahbazi Mojarrad

Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

Masoud Farshbaf

Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

Hadi Valizadeh

Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran

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