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.

Chemical Science
|June 23, 2022
PubMed

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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