Ketorolac disturbs proteasome functions and induces mitochondrial abnormality-associated apoptosis

Area of Science:

• Biochemistry
• Molecular Biology
• Oncology

Background:

• Non-steroidal anti-inflammatory drugs (NSAIDs) are commonly used for pain management.
• Previous research indicates NSAIDs may inhibit cancer cell proliferation and induce apoptosis.
• The precise molecular mechanisms of Ketorolac's anti-cancer effects remain largely undefined.

Purpose of the Study:

• To elucidate the molecular mechanisms by which Ketorolac induces apoptosis in cancer cells.
• To investigate Ketorolac's potential as an anti-tumor agent.
• To explore the role of proteasome function and protein aggregation in Ketorolac's effects.

Main Methods:

• Cellular treatment with Ketorolac.
• Analysis of proteasome function and protein aggregation (ubiquitinated and polyglutamine proteins).
• Assessment of cell cycle protein accumulation, mitochondrial membrane potential, and cytochrome c release.

Main Results:

• Ketorolac treatment disturbed proteasome function, causing aggregation of ubiquitinated and expanded polyglutamine proteins.
• Ketorolac induced accumulation of cell cycle-linked proteins, leading to apoptosis.
• Ketorolac-mediated proteasome dysfunction resulted in mitochondrial abnormalities, including membrane depolarization and cytochrome c release.

Conclusions:

• Ketorolac induces apoptosis in cancer cells through proteasome functional depletion and subsequent mitochondrial dysfunction.
• The findings highlight Ketorolac's potential as an anti-cancer agent by promoting cancer cell death.
• Further research is warranted to explore NSAID-based anti-proliferative mechanisms and combination therapies for cancer treatment.