Trigeminal star-like platinum complexes induce cancer cell senescence through quadruplex-mediated telomere...

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Biochemistry

Background:

• Telomeres protect chromosome ends but are prone to dysfunction.
• G-quadruplexes (G4) are non-canonical DNA structures implicated in telomere regulation.
• Targeting telomere G-quadruplexes (hTel G4) is a promising anticancer strategy.

Purpose of the Study:

• To synthesize novel platinum complexes for selective induction of hTel G4.
• To investigate the biological consequences of induced hTel G4 formation.

Main Methods:

• Synthesis and characterization of trigeminal star-like platinum complexes.
• In vitro assays to assess hTel G4 binding selectivity and affinity.
• Cellular studies to evaluate telomeric DNA damage response (TDDR) and senescence induction.

Main Results:

• Two novel platinum complexes demonstrated high selectivity and affinity for hTel G4.
• The induced hTel G4 formation triggered a robust TDDR.
• Significant telomere dysfunction and induction of cell senescence were observed.

Conclusions:

• Trigeminal star-like platinum complexes are effective inducers of hTel G4.
• Targeting hTel G4 with these complexes leads to telomere dysfunction and senescence.
• These findings support the development of G4-targeting agents for cancer therapy.