# Inhibiting autophagy enhances anti-cancer properties of sulforaphane

## TL;DR

Inhibiting autophagy with sulforaphane enhances the anti-cancer effects of chloroquine in bladder cancer cells.

## Contribution

The study reveals that combining sulforaphane with chloroquine improves anticancer effects by regulating autophagy-related pathways.

## Key findings

- Chloroquine reduces cancer cell migration and proliferation but increases ICAM-1 expression.
- Sulforaphane enhances chloroquine's anticancer effects by inhibiting autophagy and regulating AKT/GSK-3β and mTOR/ULK pathways.
- The combination reduces mitochondrial membrane potential and regulates ROS levels in bladder cancer cells.

## Abstract

Bladder cancer (BC) has an extremely low survival rate due to its tendency to metastasize. The antimalarial drug chloroquine (CQ) can inhibit BC progression and invasiveness by targeting basal autophagy. However, the mechanism by which CQ affects BC is not defined. Here, we revealed that although CQ showed an anticancer effect by reducing the migration and proliferation of the analyzed bladder cancer cells, it increased the expression of ICAM-1, a protein whose expression is associated with higher tumorigenic potential. Sulforaphane (SFN), a well-known ICAM-1 inhibitor, significantly contributed to the enhancement of anticancer effect of CQ, through regulation of both AKT/GSK-3β and mTOR/ULK pathways, which led to effective inhibition of autophagy, reduced proliferation level or inhibition of migration of the analyzed bladder cells. Moreover, regulation of pathways related to autophagy contributed to the reduction of mitochondrial membrane potential and regulation of ROS level. Nevertheless, the level of influence of CQ and SFN on the anticancer effects strongly depended on the molecular basis of the analyzed bladder cell lines. Our data indicate that although CQ exerts antitumor effects on bladder cancer cells, it should be noted that activation of some pro-tumor pathways may be associated with subsequent disease relapse or treatment resistance.

The online version contains supplementary material available at 10.1038/s41598-026-35891-x.