# Overcoming chemoresistance in nasopharyngeal carcinoma: minocycline as a mitochondrial translation inhibitor

## TL;DR

Minocycline, a drug that inhibits mitochondrial translation, shows promise in overcoming chemo-resistance in nasopharyngeal carcinoma.

## Contribution

Minocycline is identified as a novel mitochondrial translation inhibitor effective against chemo-resistant nasopharyngeal carcinoma cells.

## Key findings

- Minocycline selectively inhibits chemo-resistant NPC cells while sparing non-cancerous cells.
- Minocycline disrupts mitochondrial respiration by inhibiting mitochondrial translation and reducing complex I and IV activities.
- Genetic knockdown of EF-Tu and xenograft experiments validate mitochondrial translation as a therapeutic target in NPC.

## Abstract

Chemo-resistance poses a major challenge in nasopharyngeal carcinoma (NPC) treatment, necessitating novel therapeutic approaches. Through a chemical screen, we identified minocycline as a selective inhibitor of chemo-resistant NPC cells, demonstrating potent cytotoxicity while sparing non-cancerous cells. Mechanistically, minocycline inhibited mitochondrial translation, leading to reduced activities of mitochondrial complexes I and IV, impaired oxygen consumption, and disrupted mitochondrial respiration. Its cytotoxic effects were dependent on oxygen availability and an intact mitochondrial respiratory chain, as evidenced by its diminished efficacy under anoxic conditions. Genetic knockdown of mitochondrial elongation factor Tu (EF-Tu), a critical regulator of mitochondrial translation, mimicked the effects of minocycline, further validating mitochondrial translation as a therapeutic target. In a chemo-resistant NPC xenograft model, minocycline significantly suppressed tumor growth, reduced Ki-67 expression, and impaired mitochondrial function in tumor-derived cells. These findings highlight mitochondrial translation inhibition as a promising strategy to overcome chemo-resistance in NPC and identify minocycline as a potential therapeutic agent.