Intramitochondrial co-assembly between ATP and nucleopeptides induces cancer cell apoptosis
Huyeon Choi1, Gaeun Park1, Eunhye Shin2
1Department of Chemistry, Ulsan National Institute of Science and Technology (UNIST) 50 Unist-gil Ulju-gun Ulsan 44919 Republic of Korea jhryu@unist.ac.kr.
Abstract:
Mitochondria are essential intracellular organelles involved in many cellular processes, especially adenosine triphosphate (ATP) production. Since cancer cells require high ATP levels for proliferation, ATP elimination can be a unique target for cancer growth inhibition. We describe a newly developed mitochondria-targeting nucleopeptide (MNP) that sequesters ATP by self-assembling with ATP inside mitochondria. MNP interacts strongly with ATP through electrostatic and hydrogen bonding interactions. MNP exhibits higher binding affinity for ATP (-637.5 kJ mol-1) than for adenosine diphosphate (ADP) (-578.2 kJ mol-1). To improve anticancer efficacy, the small-sized MNP/ADP complex formed large assemblies with ATP inside cancer cell mitochondria. ATP sequestration and formation of large assemblies of the MNP/ADP-ATP complex inside mitochondria caused physical stress by large structures and metabolic disorders in cancer cells, leading to apoptosis. This work illustrates a facile approach to developing cancer therapeutics that relies on molecular assemblies.
Insights
Researchers developed a novel mitochondria-targeting nucleopeptide (MNP) that depletes cancer cell energy (ATP). This strategy inhibits cancer growth by inducing apoptosis through molecular self-assembly within mitochondria.
Area of Science:
- Biochemistry
- Cell Biology
- Nanotechnology
Background:
- Mitochondria are crucial for cellular energy production, particularly adenosine triphosphate (ATP).
- Cancer cells exhibit high ATP demand for proliferation, making ATP a potential therapeutic target.
- Targeting mitochondrial ATP offers a unique strategy for cancer growth inhibition.
Purpose of the Study:
- To develop and characterize a novel mitochondria-targeting nucleopeptide (MNP) for cancer therapy.
- To investigate the mechanism of MNP-mediated ATP sequestration and its effect on cancer cells.
- To explore the potential of molecular self-assembly within mitochondria as an anticancer approach.
Main Methods:
- Design and synthesis of a mitochondria-targeting nucleopeptide (MNP).
- Investigation of MNP's binding affinity and interactions with adenosine triphosphate (ATP) and adenosine diphosphate (ADP).
- In vitro studies on cancer cells to assess MNP's self-assembly, ATP sequestration, and induction of apoptosis.
Main Results:
- MNP strongly binds to ATP via electrostatic and hydrogen bonding interactions, with higher affinity for ATP than ADP.
- MNP self-assembles with ATP inside cancer cell mitochondria, forming large molecular structures.
- ATP sequestration and the formation of large MNP/ADP-ATP complexes induce physical stress and metabolic disruption, leading to cancer cell apoptosis.
Conclusions:
- MNP effectively targets mitochondria and sequesters ATP, inhibiting cancer cell proliferation.
- Self-assembly of MNP with ATP inside mitochondria represents a novel mechanism for cancer therapy.
- This approach offers a facile strategy for developing new cancer therapeutics based on molecular assemblies.
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