Synergistic anticancer effects of mitochondria-targeting peptide combined with paclitaxel in breast cancer cells: a preclinical study
10.4174/astr.2025.108.2.108
- Author:
Juneyoung AHN
1
;
Ok-Hee KIM
;
Seongeon JIN
;
Ja-Hyoung RYU
;
Dosang LEE
;
Woo-Chan PARK
;
Say-June KIM
Author Information
1. Department of Surgery, Uijeongbu St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul, Korea
- Publication Type:ORIGINAL ARTICLE
- From:Annals of Surgical Treatment and Research
2025;108(2):108-123
- CountryRepublic of Korea
- Language:English
-
Abstract:
Purpose:Mitochondria-accumulating amphiphilic peptide (Mito-FF) was designed to selectively target mitochondria in cancer cells and enhance anticancer effects through its unique structure. Mito-FF consists of (1) diphenylalanine, a β-sheet-forming building block critical for self-assembly; (2) triphenylphosphonium, a mitochondrial targeting moiety guiding the peptide to mitochondria; and (3) pyrene, a fluorescent probe enabling visualization of its accumulation and selfassembly. This study evaluates the anticancer efficacy of Mito-FF in breast cancer cells and explores its combination with paclitaxel, a standard therapy for breast cancer, focusing on its modulation of the epithelial-mesenchymal transition (EMT) pathway.
Methods:In vitro and in vivo experiments were performed using MCF-7 and MDA-MB-231 breast cancer cell lines and their respective xenograft models. Cell viability, migration, EMT marker expression, and apoptosis-related proteins were analyzed.
Results:Mito-FF demonstrated superior inhibition of cell viability and migration compared to paclitaxel alone in both cell lines. Combination therapy with Mito-FF and paclitaxel resulted in enhanced reduction of cell viability and migration. EMT markers were significantly modulated, with decreased mesenchymal markers (Snail and vimentin) and increased epithelial marker (E-cadherin) following combination treatment. Furthermore, the combination therapy synergistically elevated proapoptotic markers such as poly (adenosine diphosphate-ribose) polymerase and reduced anti-apoptotic markers such as myeloid cell leukemia 1. In vivo experiments revealed a marked reduction in tumor volume with combination therapy, accompanied by the highest expression levels of E-cadherin and pro-apoptotic marker Bim.
Conclusion:Mito-FF, designed for mitochondrial targeting and visualization, exhibited potent anticancer effects when combined with paclitaxel, in the breast cancer cells.
