In vitro mitochondrial-targeted antioxidant peptide induces apoptosis in cancer cells

• Main Authors: Zhan W, Liao X, Li L, Chen Z, Tian T, Yu L
• Format: Article
• Language: English
• Published: Dove Medical Press 2019-09-01
• Series: OncoTargets and Therapy
• Subjects: reactive oxygen species (ROS); oxidative stress; mitochondrial targeted peptide; anticancer
• Online Access: https://www.dovepress.com/in-vitro-mitochondrial-targeted-antioxidant-peptide-induces-apoptosis--peer-reviewed-article-OTT
• ISSN: 1178-6930

Wei Zhan*,1, Xin Liao*,2, Lianghe Li3, Zhongsheng Chen3, Tian Tian4, Lei Yu5, Zupeng Chen6 1Department of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, People’s Republic of China; 2Department of Imaging, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, People’s Republic of China; 3Department of Surgery, Clinical Medical College, Guizhou Medical University, Guiyang 550004, People’s Republic of China; 4Department of Pathophysiology, Basic Medical College, Guizhou Medical University, Guiyang 550004, People’s Republic of China; 5Department of Pathology, Guiyang Maternal and Child Health Hospital, Guiyang 550004, People’s Republic of China; 6Department of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310006, People’s Republic of China*These authors contributed equally to this workCorrespondence: Zupeng ChenDepartment of Neurosurgery, The First Affiliated Hospital of Zhejiang Chinese Medical University, No. 54, Youdian Road, Hangzhou 310006, People’s Republic of ChinaTel [phone]Email [e-mail]: Reactive oxygen species (ROS) are major contributors to cancer and involved in numerous tumor proliferation signaling pathways. Mitochondria are the major ROS-producing organelles, and ROS are produced from the synthesis of adenosine triphosphate and cell metabolism.Methods: A novel mitochondria-targeted peptide, namely KRSH, was synthesized and characterized. KRSH consists of four amino acids; lysine and arginine contain positively charged groups that help KRSH target the mitochondria, while tyrosine and cysteine neutralize excessive endogenous ROS, thereby inhibiting tumorigenesis.Results: The results indicated that KRSH is specifically inhibiting the growth of HeLa and MCF-7 cancer cell lines. However, MCF10A cells can resist the effects of KRSH even in a relative higher concentration. The dichloro-dihydro-fluorescein diacetate and MitoSOXTM Red assay suggested that KRSH drastically decreased the level of ROS in cancer cells. The mitochondrial depolarization assay indicated that treatment with KRSH at a dose of 50 nM may decrease the mitochondrial membrane potential leading to apoptosis of HeLa and MCF-7 cells.Conclusion: In other studies, investigating rat liver mitochondria, the uptake of KRSH may reach 80% compared with that for mitoquinone. Therefore, KRSH was designed as a superior peptide antioxidant and a mitochondria-targeting anticancer agent.Keywords: reactive oxygen species, ROS, oxidative stress, mitochondrial targeted, anticancer