Cyclometalated Iridium(III) Complex-Cationic Peptide Hybrids Trigger Paraptosis in Cancer Cells via an Intracellular...

Area of Science:

• Biochemistry
• Cell Biology
• Materials Science

Background:

• Amphiphilic Iridium complex-peptide hybrids (IPHs) demonstrate anticancer activity.
• Previous studies suggested IPHs induce non-apoptotic programmed cell death via calcium-calmodulin complex interaction.
• Paraptosis is a distinct form of programmed cell death characterized by cytoplasmic vacuolization.

Purpose of the Study:

• To elucidate the detailed mechanism of cell death induced by the IPH ASb-2.
• To compare the cell death pathways induced by ASb-2 and celastrol, a known paraptosis inducer.
• To investigate the role of endoplasmic reticulum stress and mitochondrial membrane potential in ASb-2-induced cell death.

Main Methods:

• Treatment of Jurkat cells with ASb-2 and celastrol.
• Assessment of endoplasmic reticulum (ER) stress markers.
• Measurement of mitochondrial membrane potential (ΔΨ).
• Analysis of cytoplasmic vacuolization as a hallmark of paraptosis.

Main Results:

• ASb-2 induces paraptotic programmed cell death in Jurkat cells, characterized by cytoplasmic vacuolization.
• ASb-2 treatment leads to ER stress and a decrease in mitochondrial membrane potential (ΔΨ).
• Celastrol also induces paraptosis, but with negligible changes in ΔΨ and potentially via different signaling pathways compared to ASb-2.

Conclusions:

• ASb-2 is a potent inducer of paraptotic programmed cell death in cancer cells.
• ASb-2-induced paraptosis involves ER stress and mitochondrial dysfunction.
• While both ASb-2 and celastrol induce paraptosis, their underlying molecular mechanisms differ, offering potential for targeted cancer therapies.