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Sci Rep. 2017 Aug 15;7(1):8293. doi: 10.1038/s41598-017-08963-2.

Cell surface binding, uptaking and anticancer activity of L-K6, a lysine/leucine-rich peptide, on human breast cancer MCF-7 cells.

Author information

1
Department of Pharmacy, School of Chemistry and Chemical Engineering, Liaoning Normal University, Dalian, 116029, China.
2
Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, School of Life Sciences, Liaoning Normal University, Dalian, 116081, China.
3
Liaoning Provincial Key Laboratory of Biotechnology and Drug Discovery, School of Life Sciences, Liaoning Normal University, Dalian, 116081, China. dejingshang@yahoo.com.

Abstract

Cell surface binding and internalization are critical for the specific targeting and biofunctions of some cationic antimicrobial peptides (CAPs) with anticancer activities. However, the detailed cellular process for CAPs interacting with cancer cells and the exact molecular basis for their anticancer effects are still far from being fully understood. In the present study, we examined the cell surface binding, uptaking and anti-cancer activity of L-K6, a lysine/leucine-rich CAP, in human MCF-7 breast cancer cells. We found that L-K6 preferentially interact with MCF-7 cells. This tumor-targeting property of L-K6 might be partially due to its interactions with the surface exposed and negatively charged phosphatidylserine. Subsequently, L-K6 could internalize into MCF-7 cells mainly through a clathrin-independent macropinocytosis, without significant cell surface disruption. Finally, the internalized L-K6 induced a dramatic nuclear damage and MCF-7 cell death, without significant cytoskeleton disruption and mitochondrial impairment. This cytotoxicity of L-K6 against MCF-7 cancer cells could be further confirmed by using a mouse xenograft model. In summary, all these findings outlined the cellular process and cytotoxicity of L-K6 in MCF-7 cancer cells, and might help understand the complicated interactions between CAPs and cancer cells.

PMID:
28811617
PMCID:
PMC5557901
DOI:
10.1038/s41598-017-08963-2
[Indexed for MEDLINE]
Free PMC Article

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