Anticancer activity of paroxetine in human colon cancer cells: Involvement of MET and ERBB3

Abstract

The concept of drug repositioning has recently received considerable attention in the field of oncology. In the present study, we propose that paroxetine can be used as a potent anticancer drug. Paroxetine, one of the selective serotonin reuptake inhibitors (SSRIs), has been widely prescribed for the treatment of depression and anxiety disorders. Recently, SSRIs have been reported to have anticancer activity in various types of cancer cells; however, the underlying mechanisms of their action are not yet known. In this study, we investigated the potential anticancer effect of paroxetine in human colorectal cancer cells, HCT116 and HT‐29. Treatment with paroxetine reduced cell viability, which was associated with marked increase in apoptosis, in both the cell lines. Also, paroxetine effectively inhibited colony formation and 3D spheroid formation. We speculated that the mode of action of paroxetine might be through the inhibition of two major receptor tyrosine kinases – MET and ERBB3 – leading to the suppression of AKT, ERK and p38 activation and induction of JNK and caspase‐3 pathways. Moreover, in vivo experiments revealed that treatment of athymic nude mice bearing HT‐29 cells with paroxetine remarkably suppressed tumour growth. In conclusion, paroxetine is a potential therapeutic option for patients with colorectal cancer.

Blockage of Autophagic Flux and Induction of Mitochondria Fragmentation by Paroxetine Hydrochloride in Lung Cancer Cells Promotes Apoptosis via the ROS-MAPK Pathway

“…Paxil, a widely used antidepressant, showed anti-cancer activity in various types of cancer cells such as colon cancer cells and breast cancer cells (Cho et al, 2019;Jang et al, 2019). The major kinases of MAPK pathways such as p38, JNK was proposed to mediate the drug-induced apoptosis.…”

Impact of Polypharmacy for Chronic Ailments in Colon Cancer Patients: A Review Focused on Drug Repurposing

“…Moreover, paroxetine induces cell apoptosis through MET and ERBB3 inhibition, leading to the induction of the JNK and caspase-3 pathways and the reduction of the expression of antiapoptotic protein Bcl-2 [ 62 , 63 ]. On the other hand, fluoxetine showed an antiproliferative effect on colon cancer cells by the reduction of VEGF expression [ 64 ] and by the alteration of tumour-related energy generation machinery [ 65 ], especially under conditions of hypoxia.…”

Association between selective serotonin reuptake inhibitors and kidney cancer risk: A nationwide population‐based cohort study

“…19 Compared to the prior study, we spe- The potential antineoplastic effects of SSRIs have been demonstrated in several in vitro human and animal studies. 13,14,[26][27][28][29] Most such studies have reported that fluoxetine-induced transmembrane Ca 2+ influx can result in the emptying of the endoplasmic reticulum.…”