American Association for Cancer Research
Browse
00085472can094072-sup-sfig_2.pdf (49.7 kB)

Supplementary Figure 2 from The Antidepressant Sertraline Inhibits Translation Initiation by Curtailing Mammalian Target of Rapamycin Signaling

Download (49.7 kB)
journal contribution
posted on 2023-03-30, 20:08 authored by Chen-Ju Lin, Francis Robert, Rami Sukarieh, Stephen Michnick, Jerry Pelletier
Supplementary Figure 2 from The Antidepressant Sertraline Inhibits Translation Initiation by Curtailing Mammalian Target of Rapamycin Signaling

History

ARTICLE ABSTRACT

Sertraline, a selective serotonin reuptake inhibitor, is a widely used antidepressant agent. Here, we show that sertraline also exhibits antiproliferative activity. Exposure to sertraline leads to a concentration-dependent decrease in protein synthesis. Moreover, polysome profile analysis of sertraline-treated cells shows a reduction in polysome content and a concomitant increase in 80S ribosomes. The inhibition in translation caused by sertraline is associated with decreased levels of the eukaryotic initiation factor (eIF) 4F complex, altered localization of eIF4E, and increased eIF2α phosphorylation. The latter event leads to increased REDD1 expression, which in turn impinges on the mammalian target of rapamycin (mTOR) pathway by affecting TSC1/2 signaling. Sertraline also independently targets the mTOR signaling pathway downstream of Rheb. In the Eμ-myc murine lymphoma model where carcinogenesis is driven by phosphatase and tensin homologue (PTEN) inactivation, sertraline is able to enhance chemosensitivity to doxorubicin. Our results indicate that sertraline exerts antiproliferative activity by targeting the mTOR signaling pathway in a REDD1-dependent manner. Cancer Res; 70(8); 3199–208. ©2010 AACR.

Usage metrics

    Cancer Research

    Licence

    Exports

    RefWorks
    BibTeX
    Ref. manager
    Endnote
    DataCite
    NLM
    DC