Reprograming cancer cells by a BODIPY G-quadruplex stabiliser

Area of Science:

• Medicinal Chemistry
• Molecular Biology
• Cancer Research

Background:

• G-quadruplex structures are increasingly recognized as potential therapeutic targets in cancer.
• Developing selective small molecules to stabilize G-quadruplex DNA is a promising anti-cancer strategy.
• Cancer cell migration and invasion are critical processes in metastasis that require modulation.

Purpose of the Study:

• To develop and characterize a cationic BODIPY-based molecule with selective G-quadruplex stabilizing properties.
• To evaluate the efficacy of the G-quadruplex stabilizer in inhibiting cancer cell migration and invasion.
• To investigate the impact of the stabilizer on gene expression and cellular metabolism related to metastasis.

Main Methods:

• Synthesis and characterization of a cationic BODIPY derivative.
• G-quadruplex binding affinity and selectivity assays (e.g., using fluorescence spectroscopy).
• In vitro assays to assess cancer cell migration and invasion.
• Quantitative PCR (qPCR) to measure the expression of metastasis-related genes (HIF1α, VIM, CDH1).
• Oxygen consumption rate measurements to analyze cellular metabolism.

Main Results:

• A cationic BODIPY-based G-quadruplex stabilizer was successfully developed.
• The stabilizer demonstrated significant inhibition of cancer cell migration and invasion (up to 90%).
• Modulation of critical metastasis-associated genes (HIF1α, VIM, CDH1) was observed.
• The compound reprogrammed hypoxia-adaptive metabolism, leading to a 1.82-fold increase in O2 consumption and restoration of normal energy metabolism.
• Stabilizers with high G-quadruplex affinity (Kd = 0.38 μM) showed significant anti-cancer effects.

Conclusions:

• Cationic BODIPY-based G-quadruplex stabilizers are effective in inhibiting cancer cell metastasis.
• These stabilizers offer a novel approach to targeting cancer by modulating gene expression and cellular metabolism.
• The developed G-quadruplex stabilizer represents a promising candidate for the development of small molecule anti-cancer drugs.