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Open AccessArticle

Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer

1
Department of Surgery, Eunpyeong St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 03312, Korea
2
Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST), Ulsan 44919, Korea
3
Department of Surgery, Seoul St. Mary’s Hospital, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
4
Catholic Central Laboratory of Surgery, Institute of Biomedical Industry, College of Medicine, The Catholic University of Korea, Seoul 06591, Korea
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(17), 6126; https://doi.org/10.3390/ijms21176126
Received: 16 July 2020 / Revised: 20 August 2020 / Accepted: 22 August 2020 / Published: 25 August 2020
(This article belongs to the Section Molecular Biophysics)
Here, we provide the possibility of a novel chemotherapeutic agent against gastric cancer cells, comprising the combination of 5-fluorouracil (5-FU) and a mitochondria-targeting self-assembly peptide, which is a phenylalanine dipeptide with triphenyl phosphonium (Mito-FF). The anticancer effects and mechanisms of 5-FU and Mito-FF, individually or in combination, were compared through both in vitro and in vivo models of gastric cancer. Our experiments consistently demonstrated that the 5-FU and Mito-FF combination therapy was superior to monotherapy with either, as manifested by both higher reduction of proliferation as well as an induction of apoptotic cell death. Interestingly, we found that combining 5-FU with Mito-FF leads to a significant increase of reactive oxygen species (ROS) and reduction of antioxidant enzymes in gastric cancer cells. Moreover, the inhibition of ROS abrogated the pro-apoptotic effects of combination therapy, suggesting that enhanced oxidative stress could be the principal mechanism of the action of combination therapy. We conclude that the combination of 5-FU and Mito-FF exerts potent antineoplastic activity against gastric cancer cells, primarily by promoting ROS generation and suppressing the activities of antioxidant enzymes. View Full-Text
Keywords: Mito-FF (mitochondria-accumulating phenylalanine dipeptide with triphenyl phosphonium); 5-fluorouracil; self-assembly; reactive oxygen species; antioxidant enzymes Mito-FF (mitochondria-accumulating phenylalanine dipeptide with triphenyl phosphonium); 5-fluorouracil; self-assembly; reactive oxygen species; antioxidant enzymes
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Kim, D.J.; Jeena, M.T.; Kim, O.-H.; Hong, H.-E.; Seo, H.; Ryu, J.-H.; Kim, S.-J. Novel Therapeutic Application of Self-Assembly Peptides Targeting the Mitochondria in In Vitro and In Vivo Experimental Models of Gastric Cancer. Int. J. Mol. Sci. 2020, 21, 6126.

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