In vitro mitochondrial-targeted antioxidant peptide induces apoptosis in cancer cells
Wei Zhan1, Xin Liao2, Lianghe Li3
1Department of Colorectal Surgery, The Affiliated Hospital of Guizhou Medical University, Guiyang 550004, People's Republic of China.
Introduction:
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.
Insights
A novel peptide, KRSH, targets mitochondria to reduce reactive oxygen species (ROS) and inhibit cancer cell growth. This mitochondria-targeted peptide shows promise as an antioxidant and anticancer agent.
Area of Science:
- Biochemistry
- Cell Biology
- Oncology
Background:
- Reactive oxygen species (ROS) are key drivers of cancer development, influencing tumor proliferation pathways.
- Mitochondria are primary sites of ROS production during cellular metabolism and ATP synthesis.
Purpose of the Study:
- To develop and characterize KRSH, a novel peptide designed for mitochondria targeting.
- To evaluate KRSH's efficacy in neutralizing ROS and inhibiting cancer cell growth.
Main Methods:
- Synthesis and characterization of the mitochondria-targeted peptide KRSH.
- Assessment of KRSH's effect on ROS levels and mitochondrial membrane potential in cancer cells.
- Evaluation of KRSH's impact on the proliferation of specific cancer cell lines (HeLa, MCF-7) and a non-cancerous cell line (MCF10A).
Main Results:
- KRSH specifically inhibited the growth of HeLa and MCF-7 cancer cells, while MCF10A cells showed resistance.
- KRSH significantly reduced ROS levels in cancer cells.
- Low-dose KRSH treatment (50 nM) induced apoptosis in HeLa and MCF-7 cells by decreasing mitochondrial membrane potential.
Conclusions:
- KRSH demonstrates potent anticancer activity by targeting mitochondria and reducing ROS.
- The peptide KRSH is a promising mitochondria-targeting antioxidant and anticancer agent.
- KRSH exhibits superior uptake in mitochondria compared to other agents.
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