Amit Ben Hayman, Gil-Ad Irit, Taler Michal, Bar Meytal, Zolokov Amichai, Weizman Abraham
Laboratory of Biological Psychiatry, Felsenstein Medical Research Center, Rabin Medical Center, Petah Tikva, Israel.
Eur Neuropsychopharmacol. 2009 Oct;19(10):726-34. doi: 10.1016/j.euroneuro.2009.06.003. Epub 2009 Jul 24.
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.
虽然选择性5-羟色胺再摄取抑制剂（SSRI）常用于精神科适应症，但有证据表明它们也具有抗癌特性。我们评估了其对恶性T细胞（Jurkat细胞）的体外作用，发现暴露于高浓度的舍曲林（IC50 = 9.5微摩尔）或帕罗西汀（IC50 = 18微摩尔）会使细胞活力显著降低，超过等摩尔剂量的化疗药物长春新碱和环磷酰胺（P < 0.015）。细胞毒性作用包括抑制增殖和诱导凋亡，表现为[3H]胸苷掺入减少、半胱天冬酶-3酶活性增加以及Bcl-2原癌基因表达降低。未观察到对c-Jun或ERK的影响，完整机制尚待充分阐明。当与化疗联合使用时，舍曲林（7.5微摩尔）显著增强了长春新碱和阿霉素的作用，这表明在进一步的体内研究之前，SSRI类抗抑郁药可能是化疗方案中潜在的新型化学增敏剂。
