Discovery of sertraline and its derivatives able to combat drug-resistant gastric cancer cell via inducing apoptosis

Resistance phenomena during chemotherapy of tumor has been severely hampering the applications of chemotherapeutics. Due to advantage of drug repurposing, discovery of new chemosensitizers based on approved drugs is an effect strategy to find new candidates. Herein, we found antidepressant drug ? sertraline, could sensitize drug-resistant gastric cancer cell (SGC-7901/DDP) with the IC50 value of 18.73 ?M. To understand the structure?activity relationship and improve the activity, 30 derivatives were synthesized and evaluated. The IC50 value of the best compound was improved to 5.2 ?M. Moreover, we found apoptosis induction and cell cycle arrest was the reason for the cell death of the drug-resistant cells after treatment of sertraline and derivatives, and PI3K/Akt/mTOR pathway was involved.

Automated summary

The study found that the antidepressant drug sertraline could sensitize drug-resistant gastric cancer cells, and through the synthesis and evaluation of 30 derivatives, the activity of the best compound was significantly improved. Additionally, it was discovered that apoptosis induction and cell cycle arrest were the reasons for the death of drug-resistant cells, involving the PI3K/Akt/mTOR pathway.