Effects of self-assembled cell-penetrating peptides and their nano-complexes on ABCB1 expression and activity
نویسندگان
1 Liver and Gastrointestinal Diseases Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
2 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran
3 Faculty of Pharmacy and Pharmaceutical Sciences, Katz Group Centre for Pharmacy and Health Research, University of Alberta, Edmonton, Alberta, T6G 2H5, Canada
4 Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
5 Biotechnology Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
6 Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
7 Student Research Committee, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran
8 Drug Applied Research Center and Faculty of Pharmacy, Tabriz University of Medical Sciences, Tabriz, Iran
9 Immunology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
10 College of Pharmacy, Al Ain University of Science and Technology, Al Ain 64141, UAE
doi
10.22038/ijbms.2021.51675.11727چکیده
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 B1 (ABCB1) 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 ABCB1 gene was evaluated in the A549 lung carcinoma cell line. Furthermore, the cellular uptake of designed CPPs in the A549 cell line was assessed. Results: The designed peptides, including [W4K4], [WR]3-QGR, R10, and K10 increased Dox cytotoxicity after 48 hr. Furthermore, arginine-rich peptides showed higher cellular uptake. Rhodamin123 accumulation studies illustrated that all the obtained peptides could successfully inhibit the P-gp pump. The designed peptides inhibited the ABCB1 gene expression, of which, [W4K4] resulted in the lowest expression ratio. Conclusion: [W4K4], [WR]3-QGR, R10, and K10 could successfully increase the Dox cytotoxicity by decreasing the efflux pump gene expression.
