# Potassium Iodide Induces Apoptosis in Salivary Gland Cancer Cells

## TL;DR

Potassium iodide reduces salivary gland cancer cell growth by inducing apoptosis through oxidative stress, but may increase drug resistance risks.

## Contribution

Demonstrates potassium iodide's anti-cancer effects in salivary gland cancer cells via ROS-dependent apoptosis and highlights potential risks.

## Key findings

- Potassium iodide reduces salivary gland cancer cell proliferation and viability without affecting migration.
- KI induces ROS-dependent apoptosis through BAX upregulation and Bcl-2 downregulation.
- KI treatment increases EGF in non-malignant tissues and AKT phosphorylation in cancer cells, suggesting potential drug resistance risks.

## Abstract

Salivary gland cancers (SGCs) pose a therapeutic challenge due to their aggressive nature and limited treatment options. Ion transporters, particularly the sodium/iodide symporter (SLC5A5), which transport iodine in the form of iodide anion (I−) into cells, have emerged as potential therapeutic targets in tumors of glandular origin. Our research indicates that SLC5A5 is expressed predominantly in ductal cells of human and murine SGC cells. We assessed the effects of potassium iodide (KI), a source of iodide ions. KI treatment reduced SGC cell proliferation and viability without impacting migration. KI increased ROS levels and triggered caspase-dependent apoptosis, as indicated by the upregulation of the pro-apoptotic protein BAX, downregulation of the anti-apoptotic protein Bcl-2, and induction of SGC cell shrinkage. KI did not affect NF-κB or TNF-α and SLC5A5 expression. Adding the antioxidant N-acetylcysteine reversed KI-induced growth inhibition, underscoring ROS-induced oxidative stress’s crucial role in growth inhibition. While KI administered in drinking water to mice increased epidermal growth factor (EGF) expression in non-malignant salivary gland tissues, KI decreased EGF receptor (EGFR) expression in malignant SGC cell cultures, where EGFR signaling is frequently dysregulated in SGCs but promoted AKT phosphorylation. Combining KI and anti-EGFR treatment did not yield synergistic anti-SGC cell effects. The study underscores the therapeutic potential of KI as a standalone treatment in vitro for SGC cells. However, the upregulation of EGF in non-malignant tissues and, therefore, the possibility to enhance EGFR-driven signals and AKT phosphorylation after KI treatment in cancer patients could indicate a risk of rendering SGC cells more drug resistant, warranting further investigation to optimize its clinical application.