Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells

Abstract

The anti-tumor effects of selective serotonin reuptake inhibitors (SSRIs) and serotonin and norepinephrine reuptake inhibitors (SNRIs) on several types of cancer cells have been reported. However, comparison of the anti-tumor effects of these drugs on human hepatocellular carcinoma (HepG2) cells has not been studied. We compared the anti-tumor effects of four SSRIs and two SNRIs on HepG2 cells. SSRIs and duloxetine dose-dependently decreased cell viability. Milnacipran had no effect on cell viability. The half-maximal inhibitory concentration was lower in the order of: sertraline, paroxetine, duloxetine, fluvoxamine, escitalopram, and milnacipran. Exposure to sertraline (2 µM) significantly increased caspase-3/7 activity. These results suggest that, of the agents tested here, sertraline had the highest sensitivity to HepG2 cells, and activation of the caspase pathway is involved in the anti-tumor effects of sertraline in HepG2 cells.Key words selective serotonin reuptake inhibitor; anti-tumor effect; sertraline; serotonin and norepinephrine reuptake inhibitor; human hepatocellular carcinoma cell Hepatocellular carcinoma (HCC) is the fifth most common cancer worldwide and the third most common cause of cancerbased death.

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

“…15 Kuwahara et al showed the apoptotic effect of paroxetine in human HepG2 hepatocellular carcinoma cells. 9 Consistent with the findings of these studies, our findings revealed the capacity of paroxetine to cause cell growth inhibition, cell death induction, and anticancer effect in HT29-xenografted mice.…”

“…Several classes of antidepressants, including tricyclic antidepressants (TCAs), serotonin‐norepinephrine reuptake inhibitors, and selective serotonin‐reuptake inhibitors (SSRIs), are available. Recent studies have shown that certain TCAs and SSRIs exhibit potent anticancer activities as well as psychotropic effects . In a previous epidemiological study, daily intake of SSRI was shown to reduce the risk of CRC, whereas no protective effect was found for TCAs .…”

“…Recent studies have shown that certain TCAs and SSRIs exhibit potent anticancer activities as well as psychotropic effects. 9,10 In a previous epidemiological study, daily intake of SSRI was shown to reduce the risk of CRC, whereas no protective effect was found for TCAs. 11 In addition to other drugs belonging to SSRIs (eg, fluoxetine and sertraline), paroxetine is a potent SSRI, which has proven to be effective in treating generalized anxiety and major depressive disorders.…”

The Impact of the Serotonin on the Cause and Treatment of Cancer

“…However, comparison of anti-tumor effects of SSRIs and SNRIs on HepG2 cells has not been studied. Here, we compared the anti-tumor effects of four SSRIs (escitalopram, fluvoxamine, paroxetine, sertraline) and two SNRIs (duloxetine, milnacipran) on HepG2 cells [48] . Bernhard Svejda et al mentioned that fibrosis is a cardinal feature of small intestinal neuroendocrine tumors (SI-NETs) both in local peritumoral tissue and systemic sites (cardiac).…”

Can Stopping Nerves, Stop Cancer?

“…Furthermore, common therapies for stress and anxiety disorders, such as benzodiazepines and SSRIs, also inhibit proliferation and migration of cancer cells in vitro [43-45]. Studies using in vivo models have confirmed that stress enhances tumor growth and that stress reduction, either via behavioral or pharmacological means, retards disease progression [39, 46, 47].…”