Comparison of the Anti-tumor Effects of Selective Serotonin Reuptake Inhibitors as Well as Serotonin and Norepinephrine Reuptake Inhibitors in Human Hepatocellular Carcinoma Cells.
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.
Department of Clinical Pharmacology and Biopharmaceutics, Graduate School of Pharmaceutical Sciences, Kyushu University.
Jun
J
Kuwahara
Takaaki
T
Yamada
Nobuaki
N
Egashira
Mitsuyo
M
Ueda
Nina
N
Zukeyama
Soichiro
S
Ushio
Satohiro
S
Masuda
D000970:Antineoplastic Agents / Q000494:pharmacology*; D006528:Carcinoma, Hepatocellular; D053148:Caspase 3 / Q000378:metabolism; D053179:Caspase 7 / Q000378:metabolism; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D015283:Citalopram / Q000494:pharmacology; D003521:Cyclopropanes / Q000494:pharmacology; D000068736:Duloxetine Hydrochloride / Q000494:pharmacology; D016666:Fluvoxamine / Q000494:pharmacology; D056945:Hep G2 Cells; D006801:Humans; D008113:Liver Neoplasms; D000078764:Milnacipran; D017374:Paroxetine / Q000494:pharmacology; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology*; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors / Q000494:pharmacology*; D020280:Sertraline / Q000494:pharmacology
D000970:Antineoplastic Agents; D053148:Caspase 3; D053179:Caspase 7; D015283:Citalopram; D003521:Cyclopropanes; D000068736:Duloxetine Hydrochloride; D016666:Fluvoxamine; D000078764:Milnacipran; D017374:Paroxetine; D017367:Selective Serotonin Reuptake Inhibitors; D000068760:Serotonin and Noradrenaline Reuptake Inhibitors; D020280:Sertraline