Antidepressant Drug Sertraline against Human Cancer Cells

The use of FDA-approved drugs for new indications represents a faster and more economical way to find novel therapeutic agents for cancer therapy, compared to the development of new drugs. Repurposing drugs is advantageous in a pharmacological context since these drugs already have extensive data related to their pharmacokinetics, facilitating their approval process for different diseases. Several studies have reported the promising anticancer effects of sertraline, both alone and combined, in different types of cancer cell lines. Here, we performed a literature review on the anticancer potential of sertraline against different human cancer cells, more specifically in lung, colorectal, breast, hepatocellular, leukemia, brain, skin, oral, ovarian, and prostate cancer. Taken together, these findings suggest that sertraline decreases cell viability, proliferation, migration, and invasion, induces apoptosis, and causes cell cycle arrest in different types of cancer cells, besides being an established P-glycoprotein modulator. It was also found that this drug is able to modulate autophagy, cause DNA fragmentation, and induce radical oxygen species (ROS) formation. Moreover, it was found this drug targets important cellular pathways involved in tumorigeneses such as the TNF-MAP4K4-JNK pathway, the antiapoptotic pathway PI3K/Akt/mTOR, and the AMPK/mTOR axis. This drug also interferes with the TCTP/P53 feedback loop and with the cytosolic free Ca²⁺ levels. Together, these results suggest that sertraline may be a promising compound for further evaluation in novel cancer therapies.