The SGLT2 inhibitor canagliflozin suppresses growth and enhances prostate cancer response to radiotherapy.

ABSTRACT: Radiotherapy is a non-invasive standard treatment for prostate cancer (PC). However, PC develops radio-resistance, highlighting a need for agents to improve radiotherapy response. Canagliflozin, an inhibitor of sodium-glucose co-transporter-2, is approved for use in diabetes and heart failure, but is also shown to inhibit PC growth. However, whether canagliflozin can improve radiotherapy response in PC remains unknown. Here, we show that well-tolerated doses of canagliflozin suppress proliferation and survival of androgen-sensitive and insensitive human PC cells and tumors and sensitize them to radiotherapy. Canagliflozin blocks mitochondrial respiration, promotes AMPK activity, inhibits the MAPK and mTOR-p70^S6k/4EBP1 pathways, activates cell cycle checkpoints, and inhibits prol

SUBMITTER: Ali A 

PROVIDER: S-EPMC10491589 | biostudies-literature | 2023 Sep

REPOSITORIES: biostudies-literature