Proapoptotic and chemosensitizing effects of selective serotonin reuptake inhibitors on T cell lymphoma/leukemia (Jurkat) in vitro.
While selective serotonin reuptake inhibitors (SSRIs) are commonly used for psychiatric indications, evidence implies them to possess anti-cancerous properties as well. We evaluated such in vitro effects in malignant T cells (Jurkat), finding that exposure to high concentrations of sertraline (IC(50)=9.5 microM) or paroxetine (IC(50)=18 microM) yielded a considerable reduction in cellular viability, exceeding equimolar doses of the chemotherapeutics vincristine and cyclophosphamide (P<0.015). The cytotoxic effects included both inhibition of proliferation and induction of apoptosis, demonstrated by decreased [3H] thymidine incorporation and increased activity of the caspase-3 enzyme, as well as a decrease in the expression of the Bcl-2 proto-oncogene. No effect on c-Jun or ERK was observed, rendering the complete mechanism yet to be fully elucidated. When combined with chemotherapy, sertraline (7.5 microM) markedly enhanced the effects of both vincristine and doxorubicin, suggesting SSRI antidepressants as potential new chemosensitizers in chemotherapeutic regimens, pending further in vivo research.
Amit
Ben Hayman
BH
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Gil-Ad
Irit
I
Taler
Michal
M
Bar
Meytal
M
Zolokov
Amichai
A
Weizman
Abraham
A
D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects*; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D017024:Chemotherapy, Adjuvant; D004317:Doxorubicin / Q000494:pharmacology; D004347:Drug Interactions; D006801:Humans; D019169:Jurkat Cells; D015459:Leukemia-Lymphoma, Adult T-Cell / Q000188:drug therapy*; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D017374:Paroxetine / Q000494:pharmacology; D000090063:Proto-Oncogene Mas; D017367:Selective Serotonin Reuptake Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D020280:Sertraline / Q000494:pharmacology; D014750:Vincristine / Q000494:pharmacology
D000970:Antineoplastic Agents; D004317:Doxorubicin; D020928:Mitogen-Activated Protein Kinases; D017374:Paroxetine; D000090063:Proto-Oncogene Mas; D017367:Selective Serotonin Reuptake Inhibitors; D020280:Sertraline; D014750:Vincristine; C000715470:MAS1 protein, human