Anticancer effect evaluation of iridium(III) complexes targeting mitochondria and endoplasmic reticulum

Area of Science:

• Inorganic Chemistry
• Materials Science
• Cancer Biology

Background:

• Iridium(III) complexes are explored for their photophysical properties and potential therapeutic applications.
• Developing novel metallodrugs with targeted cancer cell toxicity is a key area of research.
• Understanding the mechanism of action of these complexes is crucial for drug development.

Purpose of the Study:

• To synthesize and characterize novel iridium(III) complexes with the HMSPIP ligand.
• To evaluate the cytotoxicity and cellular mechanisms of these complexes against HeLa cancer cells.
• To investigate the potential of these complexes as candidate drugs for HeLa cancer treatment.

Main Methods:

• Synthesis and characterization of iridium(III) complexes using NMR and UV/Vis spectroscopy.
• Cytotoxicity evaluation using MTT assay, scratch wound healing, and colony-forming assays.
• Cell cycle analysis, intracellular calcium and ROS level measurements, mitochondrial membrane potential assessment, and apoptosis studies.

Main Results:

• The synthesized iridium(III) complexes, Ir1 and Ir2, demonstrated high toxicity against HeLa cells.
• Complexes induced cell cycle arrest at the G0/G1 phase.
• Cellular studies revealed ER and mitochondrial targeting, leading to increased Ca2+, ROS, decreased GSH, and apoptosis.

Conclusions:

• The iridium(III) complexes exhibit potent anticancer activity against HeLa cells through apoptosis induction.
• The mechanism involves ER and mitochondrial dysfunction, oxidative stress, and disruption of cellular redox balance.
• These complexes represent promising candidates for the development of novel therapeutic agents for HeLa cancer.